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The PSD-95 inhibitor NA-1 is delivered to the brain upon nasal administration with uptake into the olfactory bulb improved by co-administration with the cell-penetrating peptides lowPro and Tat.
Schmidt SE, Joensen G, Sandbjerg C, Thaysen M, Gammelgaard B, Schindowski K, Kristensen M. Schmidt SE, et al. Drug Deliv Transl Res. 2025 Apr 3. doi: 10.1007/s13346-025-01842-8. Online ahead of print. Drug Deliv Transl Res. 2025. PMID: 40180762
Ischemic stroke affects millions of people annually with limited treatment options targeting excitotoxicity, a major cause of cognitive impairment. The PSD-95 inhibitor NA-1 has demonstrated neuroprotective potential, but its efficacy via intrav …
Ischemic stroke affects millions of people annually with limited treatment options targeting excitotoxicity, a major cause of …
Comparison of Noncontrast Computed Tomography, Multiphase Computed Tomography Angiography, and Computed Tomography Perfusion to Assess Infarct Growth Rate in Acute Stroke.
Pensato U, Bosshart SL, Stebner A, Dowlatshahi D, Bang OY, Sahlas DJ, Field TS, Puetz V, Buck BH, Hill MD, Goyal M, Demchuk AM, Ospel JM. Pensato U, et al. Stroke. 2025 Mar;56(3):657-666. doi: 10.1161/STROKEAHA.124.047680. Epub 2025 Feb 10. Stroke. 2025. PMID: 39925291 Clinical Trial.
BACKGROUND: Infarct growth rate is remarkably heterogeneous in acute ischemic stroke, reflecting diverse clinical-physiological phenotypes. We compared different methods of estimating infarct growth rate in patients with acute ischemic stroke undergoin …
BACKGROUND: Infarct growth rate is remarkably heterogeneous in acute ischemic stroke, reflecting diverse clinical-physiologica …
Comparative efficacy of neuroprotective agents for improving neurological function and prognosis in acute ischemic stroke: a network meta-analysis.
Wang Y, Li M, Jiang Y, Ji Q. Wang Y, et al. Front Neurosci. 2025 Jan 6;18:1530987. doi: 10.3389/fnins.2024.1530987. eCollection 2024. Front Neurosci. 2025. PMID: 39834702 Free PMC article.
BACKGROUND: Ischemic stroke is the second leading cause of death and the third leading cause of combined disability and mortality globally. While reperfusion therapies play a critical role in the management of acute ischemic stroke (AIS), their applica …
BACKGROUND: Ischemic stroke is the second leading cause of death and the third leading cause of combined disability and mortal …
SMP30 alleviates cerebral ischemia/reperfusion-induced neuronal injury by inhibiting HDAC4/PSD-95 to preserve mitochondrial function.
Chen R, Qian L, Zhang Q, Qin J, Chen X, Xu X. Chen R, et al. J Neuropathol Exp Neurol. 2025 Jan 1;84(1):59-73. doi: 10.1093/jnen/nlae095. J Neuropathol Exp Neurol. 2025. PMID: 39254519
Ischemic stroke is a major cause of global death and permanent disability. Major consequences of ischemic stroke include neuronal mitochondrial dysfunction. ...Together, these findings indicate that SMP30 alleviates cerebral I/R-induced neuronal injury …
Ischemic stroke is a major cause of global death and permanent disability. Major consequences of ischemic stroke …
Neuroprotective strategies in acute ischemic stroke: A narrative review of recent advances and clinical outcomes.
Zhao M, Qiao Y, Weiss A, Zhao W. Zhao M, et al. Brain Circ. 2024 Dec 28;10(4):296-302. doi: 10.4103/bc.bc_165_24. eCollection 2024 Oct-Dec. Brain Circ. 2024. PMID: 40012592 Free PMC article. Review.
Reperfusion therapy, which substantially promotes the vessel recanalization rate and improves clinical outcomes, remains the most effective treatment of acute ischemic stroke (AIS). However, a substantial number of patients are either unsuitable for recanalization t …
Reperfusion therapy, which substantially promotes the vessel recanalization rate and improves clinical outcomes, remains the most effective …
Prevalence of ipsilateral "vulnerable carotid plaques with <50 % stenosis" on CT angiography in embolic stroke of undetermined source.
Uchida K, Bosshart S, Stebner A, Almekhlafi MA, Demchuk AM, Ganesh A, Buck B, Poppe AY, Singh N, Marko M, Hill MD, Goyal M, Ospel JM. Uchida K, et al. J Neurol Sci. 2024 Dec 15;467:123316. doi: 10.1016/j.jns.2024.123316. Epub 2024 Nov 20. J Neurol Sci. 2024. PMID: 39580929 Free article. Clinical Trial.
BACKGROUND: Carotid plaques may be an important etiology in ischemic stroke. We aimed to assess carotid plaque characteristics ipsilateral and contralateral to the ischemic stroke and assessed the prevalence of "vulnerable carotid plaques with <50% …
BACKGROUND: Carotid plaques may be an important etiology in ischemic stroke. We aimed to assess carotid plaque characteristics …
Design of peptide therapeutics as protein-protein interaction inhibitors to treat neurodegenerative diseases.
Ariawan D, Thananthirige KPM, El-Omar A, van der Hoven J, Genoud S, Stefen H, Fath T, van Eersel J, Ittner LM, Tietz O. Ariawan D, et al. RSC Adv. 2024 Oct 30;14(47):34637-34642. doi: 10.1039/d4ra05040a. eCollection 2024 Oct 29. RSC Adv. 2024. PMID: 39479480 Free PMC article.
Peptide therapeutics are an emerging class of drugs to treat neurodegenerative diseases by inhibiting protein-protein interactions (PPIs). Nerinetide has recently emerged as a promising therapeutic for the treatment of ischemic stroke and Alzheimer's Disease …
Peptide therapeutics are an emerging class of drugs to treat neurodegenerative diseases by inhibiting protein-protein interactions (PPIs). …
The DNA repair protein DNA-PKcs modulates synaptic plasticity via PSD-95 phosphorylation and stability.
Mollinari C, Cardinale A, Lupacchini L, Martire A, Chiodi V, Martinelli A, Rinaldi AM, Fini M, Pazzaglia S, Domenici MR, Garaci E, Merlo D. Mollinari C, et al. EMBO Rep. 2024 Aug;25(8):3707-3737. doi: 10.1038/s44319-024-00198-3. Epub 2024 Jul 31. EMBO Rep. 2024. PMID: 39085642 Free PMC article.
Here we show that DNA-PKcs modulates synaptic plasticity. We demonstrate that DNA-PKcs localizes at synapses and phosphorylates PSD-95 at newly identified residues controlling PSD-95 protein stability. DNA-PKcs -/- mice are characterized by impa …
Here we show that DNA-PKcs modulates synaptic plasticity. We demonstrate that DNA-PKcs localizes at synapses and phosphorylates PS …
HERMES-24 Score Derivation and Validation for Simple and Robust Outcome Prediction After Large Vessel Occlusion Treatment.
Tanaka K, Brown S, Goyal M, Menon BK, Campbell BCV, Mitchell PJ, Jovin TG, Saver JL, Muir KW, White PM, Bracard S, Guillemin F, Roos YBWEM, van Zwam WH, Najm M, Dowlatshahi D, Hill MD, Demchuk AM; HERMES Collaborators. Tanaka K, et al. Stroke. 2024 Aug;55(8):1982-1990. doi: 10.1161/STROKEAHA.123.045871. Epub 2024 Jul 22. Stroke. 2024. PMID: 39038101 Free article.
We aimed to develop a simple outcome prediction score applied 24 hours after anterior circulation acute ischemic stroke treatment with endovascular thrombectomy and validate it in patients treated both with and without endovascular thrombectomy. ...The score was val …
We aimed to develop a simple outcome prediction score applied 24 hours after anterior circulation acute ischemic stroke treatm …
Tat-NR2B9c attenuates oxidative stress via inhibition of PSD95-NR2B-nNOS complex after subarachnoid hemorrhage in rats.
Zhang H, Xu L, He Y, Zhang Z, Zhang J, Yu Q, Liu Y, Wang X, Zhang A, Wang K, Fang Y, Chen S. Zhang H, et al. Neuropharmacology. 2024 Jun 15;251:109905. doi: 10.1016/j.neuropharm.2024.109905. Epub 2024 Mar 21. Neuropharmacology. 2024. PMID: 38521229
Moreover, Tat-NR2B9c attenuated excitotoxicity by inhibiting the interaction of PSD95-NR2B-nNOS. ...Tat-NR2B9c may serve as a potential treatment for SAH induced brain injury....
Moreover, Tat-NR2B9c attenuated excitotoxicity by inhibiting the interaction of PSD95-NR2B-nNOS. ...Tat-NR2B9c m …
[Repeated mild traumatic brain injury in the parietal cortex inhibits expressions of NLG-1 and PSD-95 in the medulla oblongata of mice].
Li M, He L, Li T, Bao Y, Xu X, Chen G. Li M, et al. Nan Fang Yi Ke Da Xue Xue Bao. 2024 May 20;44(5):960-966. doi: 10.12122/j.issn.1673-4254.2024.05.18. Nan Fang Yi Ke Da Xue Xue Bao. 2024. PMID: 38862454 Free PMC article. Chinese.
OBJECTIVE: To assess the effects of repeated mild traumatic brain injury (rmTBI) in the parietal cortex on neuronal morphology and synaptic plasticity in the medulla oblongata of mice. ...The mice surviving rmTBI showed significantly reduced NSS, delay …
OBJECTIVE: To assess the effects of repeated mild traumatic brain injury (rmTBI) in the parietal cortex on neuronal mor …
Neuroprotection during Thrombectomy for Acute Ischemic Stroke: A Review of Future Therapies.
Dammavalam V, Lin S, Nessa S, Daksla N, Stefanowski K, Costa A, Bergese S. Dammavalam V, et al. Int J Mol Sci. 2024 Jan 10;25(2):891. doi: 10.3390/ijms25020891. Int J Mol Sci. 2024. PMID: 38255965 Free PMC article. Review.
Advances in multiple neuroprotective therapies, including uric acid, activated protein C, nerinetide, otaplimastat, imatinib, verapamil, butylphthalide, edaravone, nelonemdaz, ApTOLL, regional hypothermia, remote ischemic conditioning, normobaric oxygen, and especia …
Advances in multiple neuroprotective therapies, including uric acid, activated protein C, nerinetide, otaplimastat, imatinib, verapam …
PSD-95 inhibitor Tat-NR2B9c (NA-1) protects the integrity of the blood-brain barrier after transient middle artery occlusion in rats by downregulating matrix metalloprotease-9 and upregulating endothelial nitric oxide synthase.
Xu Y, Xu L, Xu C, Zhao M, Xu T, Xia L, Wu Y, Cao Y, Han Z. Xu Y, et al. Brain Res Bull. 2024 Jan;206:110836. doi: 10.1016/j.brainresbull.2023.110836. Epub 2023 Dec 1. Brain Res Bull. 2024. PMID: 38042504 Free article.
Here we explored whether the PSD-95 inhibitor Tat-NR2B9c (NA-1) can protect not only neurons but also the blood-brain barrier. METHODS: Adult male Sprague-Dawley rats were randomly divided into three groups, which were subjected to either sham s …
Here we explored whether the PSD-95 inhibitor Tat-NR2B9c (NA-1) can protect not only neurons but also the …
Impact of vessel tortuosity and radiological thrombus characteristics on the choice of first-line thrombectomy strategy: Results from the ESCAPE-NA1 trial.
Bala F, Cimflova P, Singh N, Zhang J, Kappelhof M, Kim BJ, Najm M, Golan R, Elebute I, Benali F, Terreros NA, Marquering H, Majoie C, Almekhlafi M, Goyal M, Hill MD, Qiu W, Menon BK. Bala F, et al. Eur Stroke J. 2023 Sep;8(3):675-683. doi: 10.1177/23969873231183766. Epub 2023 Jun 22. Eur Stroke J. 2023. PMID: 37345551 Free PMC article.
INTRODUCTION: Despite improvements in device technology, only one-third of stroke patients undergoing endovascular thrombectomy (EVT) achieve first-pass effect (FPE). ...PATIENTS AND METHODS: Patients with thin-slice baseline CT-angiography from the ESCAPE-NA1 trial (Effic …
INTRODUCTION: Despite improvements in device technology, only one-third of stroke patients undergoing endovascular thrombectomy (EVT) …
Hypothalamic Corticotropin-Releasing Hormone Contributes to Hypertension in Spontaneously Hypertensive Rats.
Zhang H, Zhou JJ, Shao JY, Sheng ZF, Wang J, Zheng P, Kang X, Liu Z, Cheng ZJ, Kline DD, Li DP. Zhang H, et al. J Neurosci. 2023 Jun 14;43(24):4513-4524. doi: 10.1523/JNEUROSCI.2343-22.2023. Epub 2023 May 9. J Neurosci. 2023. PMID: 37160364 Free PMC article.
CRH induced a more significant increase in the firing rate of PVN-rostral ventrolateral medulla (RVLM) neurons and sympathoexcitatory response in SHRs than in WKY rats, an effect that was blocked by preapplication of NMDA receptors (NMDARs) antagonist AP5 and PSD-95 …
CRH induced a more significant increase in the firing rate of PVN-rostral ventrolateral medulla (RVLM) neurons and sympathoexcitatory respon …
Automated Segmentation of Intracranial Thrombus on NCCT and CTA in Patients with Acute Ischemic Stroke Using a Coarse-to-Fine Deep Learning Model.
Zhu K, Bala F, Zhang J, Benali F, Cimflova P, Kim BJ, McDonough R, Singh N, Hill MD, Goyal M, Demchuk A, Menon BK, Qiu W. Zhu K, et al. AJNR Am J Neuroradiol. 2023 Jun;44(6):641-648. doi: 10.3174/ajnr.A7878. Epub 2023 May 18. AJNR Am J Neuroradiol. 2023. PMID: 37202113 Free PMC article.
BACKGROUND AND PURPOSE: Identifying the presence and extent of intracranial thrombi is crucial in selecting patients with acute ischemic stroke for treatment. This article aims to develop an automated approach to quantify thrombus on NCCT and CTA in patients with …
BACKGROUND AND PURPOSE: Identifying the presence and extent of intracranial thrombi is crucial in selecting patients with acute ischemic …
Neuroprotection for Nonarteritic Central Retinal Artery Occlusion: Lessons from Acute Ischemic Stroke.
Okonkwo ON, Agweye CT, Akanbi T. Okonkwo ON, et al. Clin Ophthalmol. 2023 May 31;17:1531-1543. doi: 10.2147/OPTH.S403433. eCollection 2023. Clin Ophthalmol. 2023. PMID: 37284058 Free PMC article. Review.
Nonarteritic central retinal artery occlusion (NA-CRAO) is a variant of acute ischemic stroke (AIS) and is a cause of sudden severe loss of vision. There are guidelines by the American Heart Association and the American Stroke Association for the care of CRAO …
Nonarteritic central retinal artery occlusion (NA-CRAO) is a variant of acute ischemic stroke (AIS) and is a cause of sudden s …
Enhanced AMPAR-dependent synaptic transmission by S-nitrosylation in the vmPFC contributes to chronic inflammatory pain-induced persistent anxiety in mice.
Chen ZJ, Su CW, Xiong S, Li T, Liang HY, Lin YH, Chang L, Wu HY, Li F, Zhu DY, Luo CX. Chen ZJ, et al. Acta Pharmacol Sin. 2023 May;44(5):954-968. doi: 10.1038/s41401-022-01024-z. Epub 2022 Dec 2. Acta Pharmacol Sin. 2023. PMID: 36460834 Free PMC article.
Moreover, administration of ZL006, a small molecular inhibitor disrupting the interaction of nNOS and PSD-95 (20 mg.kg(-1).d(-1), for 5 days, i.p.), significantly reduced nitric oxide production and S-nitrosylation of AMPAR-interacting proteins in the vmPFC, resulti …
Moreover, administration of ZL006, a small molecular inhibitor disrupting the interaction of nNOS and PSD-95 (20 mg.kg(-1).d(- …
Distal Embolization in Relation to Radiological Thrombus Characteristics, Treatment Details, and Functional Outcome.
Bala F, Kappelhof M, Ospel JM, Cimflova P, Qiu W, Singh N, Zhu K, Kim BJ, Wadhwa A, Almekhlafi MA, Menon BK, Arrarte Terreros N, Marquering H, Majoie C, Hill MD, Goyal M; ESCAPE-NA1 Investigators. Bala F, et al. Stroke. 2023 Feb;54(2):448-456. doi: 10.1161/STROKEAHA.122.040542. Epub 2023 Jan 23. Stroke. 2023. PMID: 36689583
METHODS: Patients with thin-slice (2.5 mm) baseline noncontrast computed tomography and computed tomography angiography from the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) were included. Thrombus annotation …
METHODS: Patients with thin-slice (2.5 mm) baseline noncontrast computed tomography and computed tomography angiography from the ESCAPE-NA1 …
Development of a Potent Cyclic Peptide Inhibitor of the nNOS/PSD-95 Interaction.
Balboa JR, Essig DJ, Ma S, Karer N, Clemmensen LS, Pedersen SW, Joerger AC, Knapp S, Østergaard S, Strømgaard K. Balboa JR, et al. J Med Chem. 2023 Jan 12;66(1):976-990. doi: 10.1021/acs.jmedchem.2c01803. Epub 2022 Dec 29. J Med Chem. 2023. PMID: 36580549
The complex between the N-methyl-d-aspartate receptor (NMDAR), neuronal nitric oxide synthase (nNOS), and the postsynaptic density protein-95 (PSD-95) is an attractive therapeutic target for the treatment of acute ischemic stroke. ...However, nNOS bind …
The complex between the N-methyl-d-aspartate receptor (NMDAR), neuronal nitric oxide synthase (nNOS), and the postsynaptic density protein-9 …
Ischemic Stroke, Lessons from the Past towards Effective Preclinical Models.
Amado B, Melo L, Pinto R, Lobo A, Barros P, Gomes JR. Amado B, et al. Biomedicines. 2022 Oct 13;10(10):2561. doi: 10.3390/biomedicines10102561. Biomedicines. 2022. PMID: 36289822 Free PMC article. Review.
Ischemic stroke is a leading cause of death worldwide, mainly in western countries. So far, approved therapies rely on reperfusion of the affected brain area, by intravenous thrombolysis or mechanical thrombectomy. ...Recently, a brain-protective drug-nerinetide …
Ischemic stroke is a leading cause of death worldwide, mainly in western countries. So far, approved therapies rely on reperfu …
Lithium upregulates growth-associated protein-43 (GAP-43) and postsynaptic density-95 (PSD-95) in cultured neurons exposed to oxygen-glucose deprivation and improves electrophysiological outcomes in rats subjected to transient focal cerebral ischemia following a long-term recovery period.
Tai SH, Huang SY, Chao LC, Lin YW, Huang CC, Wu TS, Shan YS, Lee AH, Lee EJ. Tai SH, et al. Neurol Res. 2022 Oct;44(10):870-878. doi: 10.1080/01616412.2022.2056817. Epub 2022 Mar 29. Neurol Res. 2022. PMID: 35348035
OBJECTIVES: Lithium has numerous neuroplastic and neuroprotective effects in patients with stroke. Here, we evaluated whether delayed and short-term lithium treatment reduces brain infarction volume and improves electrophysiological and neurobehavioral outcomes following l …
OBJECTIVES: Lithium has numerous neuroplastic and neuroprotective effects in patients with stroke. Here, we evaluated whether delayed …
Quantifying the amount of greater brain ischemia protection time with pre-hospital vs. in-hospital neuroprotective agent start.
Matossian V, Starkman S, Sanossian N, Stratton S, Eckstein M, Conwit R, Liebeskind DS, Sharma L, Tenser MK, Saver JL. Matossian V, et al. Front Neurol. 2022 Sep 13;13:990339. doi: 10.3389/fneur.2022.990339. eCollection 2022. Front Neurol. 2022. PMID: 36176566 Free PMC article.
In order to do this, a comparative analysis was performed of two randomized trials of neuroprotective agents: (1) pre-hospital strategy: Field administration of stroke therapy-magnesium (FAST-MAG) Trial; (2) in-hospital strategy: Efficacy and safety of nerinetide fo …
In order to do this, a comparative analysis was performed of two randomized trials of neuroprotective agents: (1) pre-hospital strategy: Fie …
Assessment of the safety of the cationic arginine-rich peptides (CARPs) poly-arginine-18 (R18 and R18D) in ex vivo models of mast cell degranulation and red blood cell hemolysis.
Edwards AB, Mastaglia FL, Knuckey NW, Yip KH, Meloni B. Edwards AB, et al. Biochem Biophys Rep. 2022 Jul 1;31:101305. doi: 10.1016/j.bbrep.2022.101305. eCollection 2022 Sep. Biochem Biophys Rep. 2022. PMID: 35812346 Free PMC article.
Similarly, TAT-NR2B9c and protamine did not induce significant mast cell degranulation. To examine hemolytic effects, red blood cells (RBCs), were incubated with the peptides at a concentration range of 1-16 muM in the absence or presence of 2% plasma. ...This study …
Similarly, TAT-NR2B9c and protamine did not induce significant mast cell degranulation. To examine hemolytic effects, red bloo …
Inhibition of the NR2B-PSD95 Interaction Exerts Neuroprotective Effects on Retinal Ischemia-Reperfusion Injury.
Zhang X, Zhang R, Wu J. Zhang X, et al. Neuroscience. 2022 May 10;490:89-99. doi: 10.1016/j.neuroscience.2022.02.030. Epub 2022 Mar 4. Neuroscience. 2022. PMID: 35257794
Increased levels of NR2B and p-NR2B were also detected in the rat chronic ocular hypertension (COH) model, while decreased PSD95 levels accompanied by severe injury were observed. Tat-NR2B9c treatment significantly increased RGC survival in the I/R injury model by d …
Increased levels of NR2B and p-NR2B were also detected in the rat chronic ocular hypertension (COH) model, while decreased PSD95 levels acco …
Pharmacological brain cytoprotection in acute ischaemic stroke - renewed hope in the reperfusion era.
Fisher M, Savitz SI. Fisher M, et al. Nat Rev Neurol. 2022 Apr;18(4):193-202. doi: 10.1038/s41582-021-00605-6. Epub 2022 Jan 25. Nat Rev Neurol. 2022. PMID: 35079135 Free PMC article. Review.
For over 40 years, attempts to develop treatments that protect neurons and other brain cells against the cellular and biochemical consequences of cerebral ischaemia in acute ischaemic stroke (AIS) have been unsuccessful. However, the advent of intravenous thr …
For over 40 years, attempts to develop treatments that protect neurons and other brain cells against the cellular and biochemical consequenc …
PRIMED(2) Preclinical Evidence Scoring Tool to Assess Readiness for Translation of Neuroprotection Therapies.
Bahr-Hosseini M, Bikson M, Iacoboni M, Liebeskind DS, Hinman JD, Carmichael ST, Saver JL. Bahr-Hosseini M, et al. Transl Stroke Res. 2022 Apr;13(2):222-227. doi: 10.1007/s12975-021-00922-4. Epub 2021 Jul 1. Transl Stroke Res. 2022. PMID: 34196953 Free PMC article.
Once constructed, the tool was applied by two independent raters to four current candidate acute stroke therapies, including two pharmacologic agents [nerinetide and trans-sodium crocetinate] and two device interventions [cathodal transcranial direct current stimula …
Once constructed, the tool was applied by two independent raters to four current candidate acute stroke therapies, including two phar …
Systematic Review - Combining Neuroprotection With Reperfusion in Acute Ischemic Stroke.
Vos EM, Geraedts VJ, van der Lugt A, Dippel DWJ, Wermer MJH, Hofmeijer J, van Es ACGM, Roos YBWEM, Peeters-Scholte CMPCD, van den Wijngaard IR. Vos EM, et al. Front Neurol. 2022 Mar 17;13:840892. doi: 10.3389/fneur.2022.840892. eCollection 2022. Front Neurol. 2022. PMID: 35370911 Free PMC article.
BACKGROUND: Clinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be a necessary condition for positive effects of neuroprotective treatments. ...Treatment was associated with improved clinical …
BACKGROUND: Clinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Repe …
Intravenous administration of Tat-NR2B9c peptide, a PSD95 inhibitor, attenuates reinstatement of cocaine-seeking behavior in rats.
Smaga I, Wydra K, Witek K, Surówka P, Suder A, Pieniążek R, Caffino L, Fumagalli F, Sanak M, Filip M. Smaga I, et al. Behav Brain Res. 2022 Jan 7;416:113537. doi: 10.1016/j.bbr.2021.113537. Epub 2021 Aug 17. Behav Brain Res. 2022. PMID: 34416299 Free article.
Since the GluN2B subunit is stabilized at synaptic level by the interaction with its scaffolding protein PSD95, in this study we aimed at investigating efficacy of Tat-NR2B9c peptide, a PSD95 inhibitor, which disrupts the interaction of PSD95 with GluN2B, in the att …
Since the GluN2B subunit is stabilized at synaptic level by the interaction with its scaffolding protein PSD95, in this study we aimed at in …
PSD-95: An Effective Target for Stroke Therapy Using Neuroprotective Peptides.
Ugalde-Triviño L, Díaz-Guerra M. Ugalde-Triviño L, et al. Int J Mol Sci. 2021 Nov 22;22(22):12585. doi: 10.3390/ijms222212585. Int J Mol Sci. 2021. PMID: 34830481 Free PMC article. Review.
However, recent results have provided strong evidence that postsynaptic density protein-95 (PSD-95) can be exploited as an efficient target for stroke neuroprotection by strategies able to counteract excitotoxicity, a major mechanism of neuronal death …
However, recent results have provided strong evidence that postsynaptic density protein-95 (PSD-95) can be exploited as an eff …
Emerging agents for the treatment and prevention of stroke: progress in clinical trials.
Safouris A, Magoufis G, Tsivgoulis G. Safouris A, et al. Expert Opin Investig Drugs. 2021 Oct;30(10):1025-1035. doi: 10.1080/13543784.2021.1985463. Epub 2021 Oct 13. Expert Opin Investig Drugs. 2021. PMID: 34555978 Review.
EXPERT OPINION: Current approaches in stroke treatment and stroke prevention have already transformed stroke care from a linear one-for-all treatment paradigm to a more individualized approach that targets specific patient subgroups with novel pharmaceutical …
EXPERT OPINION: Current approaches in stroke treatment and stroke prevention have already transformed stroke care from …
Stroke injury induced by distal middle cerebral artery occlusion is resistant to N-methyl-d-aspartate receptor antagonism in FVB/NJ mice.
Liu CW, Liao KH, Wu CM, Chen HY, Wang EY, Lai TW. Liu CW, et al. Neuroreport. 2021 Sep 8;32(13):1122-1127. doi: 10.1097/WNR.0000000000001697. Neuroreport. 2021. PMID: 34284452
Although N-methyl-d-aspartate receptor (NMDAR) antagonism has been shown to have a neuroprotective effect in many preclinical stroke models, the efficacy of this antiexcitotoxicity strategy in clinical trials in stroke patients has been disappointing. ...In addition …
Although N-methyl-d-aspartate receptor (NMDAR) antagonism has been shown to have a neuroprotective effect in many preclinical stroke …
Neuroprotection of sevoflurane against ischemia/reperfusion-induced brain injury through inhibiting GluN2A/GluN2B-PSD-95-MLK3 module.
Jin L, Bo XM. Jin L, et al. Exp Brain Res. 2021 Sep;239(9):2701-2709. doi: 10.1007/s00221-021-06157-x. Epub 2021 Jul 5. Exp Brain Res. 2021. PMID: 34223957
Immunoblot and immunoprecipitation were used to detect the tyrosine phosphorylation of GluN2A/GluN2B, the interaction of GluN2A/GluN2B-PSD-95-MLK3 and the expression of phosphorylation of MLK3, MKK7 and JNK3. Cresyl violet staining was employed to analyse neuronal i …
Immunoblot and immunoprecipitation were used to detect the tyrosine phosphorylation of GluN2A/GluN2B, the interaction of GluN2A/GluN2B-PS …
PSD-95 protects the pancreas against pathological damage through p38 MAPK signaling pathway in acute pancreatitis.
Guo Y, Hu W, Wang X, Li C, Cui T, Liu R, He J, Yin C. Guo Y, et al. Exp Biol Med (Maywood). 2021 Jul;246(13):1473-1482. doi: 10.1177/15353702211003293. Epub 2021 Apr 1. Exp Biol Med (Maywood). 2021. PMID: 33794695 Free PMC article.
PSD-95 expression increased at 2 h, reaching the peak at 6 h in mice and 12 h in AR42J cells. ...The pancreatic histopathologic score was greater in the PSD-95 inhibition group compared with the control (P < 0.05), while it was lesser when ph …
PSD-95 expression increased at 2 h, reaching the peak at 6 h in mice and 12 h in AR42J cells. ...The pancreatic histopathologi …
NMDAR-dependent long-term depression is associated with increased short term plasticity through autophagy mediated loss of PSD-95.
Compans B, Camus C, Kallergi E, Sposini S, Martineau M, Butler C, Kechkar A, Klaassen RV, Retailleau N, Sejnowski TJ, Smit AB, Sibarita JB, Bartol TM Jr, Perrais D, Nikoletopoulou V, Choquet D, Hosy E. Compans B, et al. Nat Commun. 2021 May 14;12(1):2849. doi: 10.1038/s41467-021-23133-9. Nat Commun. 2021. PMID: 33990590 Free PMC article.
While both LTDs are associated with a loss and reorganization of synaptic AMPARs, only NMDAR-dependent LTD induction triggers a profound reorganization of PSD-95. This modification, which requires the autophagy machinery to remove the T19-phosphorylated form of P …
While both LTDs are associated with a loss and reorganization of synaptic AMPARs, only NMDAR-dependent LTD induction triggers a profound reo …
A novel cell-penetrating peptide targeting calpain-cleavage of PSD-95 induced by excitotoxicity improves neurological outcome after stroke.
Ayuso-Dolado S, Esteban-Ortega GM, Vidaurre ÓG, Díaz-Guerra M. Ayuso-Dolado S, et al. Theranostics. 2021 May 3;11(14):6746-6765. doi: 10.7150/thno.60701. eCollection 2021. Theranostics. 2021. PMID: 34093851 Free PMC article.
Interference of PSD-95 processing induced by excitotoxicity might thus be a therapeutic target for stroke and other excitotoxicity-associated pathologies. ...Conclusions: Interference of excitotoxicity-induced PSD-95-processing with specific CPP …
Interference of PSD-95 processing induced by excitotoxicity might thus be a therapeutic target for stroke and other exc …
Neuroprotective Effects Against Cerebral Ischemic Injury Exerted by Dexmedetomidine via the HDAC5/NPAS4/MDM2/PSD-95 Axis.
Lv H, Li Y, Cheng Q, Chen J, Chen W. Lv H, et al. Mol Neurobiol. 2021 May;58(5):1990-2004. doi: 10.1007/s12035-020-02223-7. Epub 2021 Jan 7. Mol Neurobiol. 2021. PMID: 33411316
Cell viability and apoptosis were assessed with the application of CCK-8 and flow cytometry. The interaction between MDM2 and PSD-95 was evaluated using Co-IP assay, followed by ubiquitination of PSD-95 detection. ...DEX plays a neuroprotective role ag …
Cell viability and apoptosis were assessed with the application of CCK-8 and flow cytometry. The interaction between MDM2 and PSD- …
Identification of Novel Fragments Binding to the PDZ1-2 Domain of PSD-95.
Zang J, Ye F, Solbak SMØ, Høj LJ, Zhang M, Bach A. Zang J, et al. ChemMedChem. 2021 Mar 18;16(6):949-954. doi: 10.1002/cmdc.202000865. Epub 2020 Dec 30. ChemMedChem. 2021. PMID: 33305877
Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules again …
Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with pep …
Spine dynamics of PSD-95-deficient neurons in the visual cortex link silent synapses to structural cortical plasticity.
Yusifov R, Tippmann A, Staiger JF, Schlüter OM, Löwel S. Yusifov R, et al. Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2022701118. doi: 10.1073/pnas.2022701118. Proc Natl Acad Sci U S A. 2021. PMID: 33649238 Free PMC article.
Consequently, in mouse primary visual cortex (V1), impaired silent synapse maturation in PSD-95-deficient neurons prevents the closure of the CP for juvenile ocular dominance plasticity (jODP). ...A similar increase in spine elimination after MD occurred if …
Consequently, in mouse primary visual cortex (V1), impaired silent synapse maturation in PSD-95-deficient neurons prevents the …
Elevated PSD-95 Blocks Ion-flux Independent LTD: A Potential New Role for PSD-95 in Synaptic Plasticity.
Dore K, Malinow R. Dore K, et al. Neuroscience. 2021 Feb 21;456:43-49. doi: 10.1016/j.neuroscience.2020.02.020. Epub 2020 Feb 28. Neuroscience. 2021. PMID: 32114099 Free PMC article.
We recently demonstrated that NMDA receptors (NMDARs) are capable of ion-flux independent signaling through conformational change in the NMDAR intracellular domain resulting in long-term depression of synaptic transmission (LTD). Here we show that PSD-95 overexpress …
We recently demonstrated that NMDA receptors (NMDARs) are capable of ion-flux independent signaling through conformational change in the NMD …
The future of neuroprotection in stroke.
Chamorro Á, Lo EH, Renú A, van Leyen K, Lyden PD. Chamorro Á, et al. J Neurol Neurosurg Psychiatry. 2021 Feb;92(2):129-135. doi: 10.1136/jnnp-2020-324283. Epub 2020 Nov 4. J Neurol Neurosurg Psychiatry. 2021. PMID: 33148815 Review.
Investigators acknowledge the limitations of rodent or non-human primate stroke models, hundreds of putative neuroprotectants have been evaluated in preclinical models, but not one has entered the clinical realm. ...At the bedside in the last 5 years, uric acid and neri …
Investigators acknowledge the limitations of rodent or non-human primate stroke models, hundreds of putative neuroprotectants have be …
Neuroprotective Cationic Arginine-Rich Peptides (CARPs): An Assessment of Their Clinical Safety.
Edwards AB, Mastaglia FL, Knuckey NW, Meloni BP. Edwards AB, et al. Drug Saf. 2020 Oct;43(10):957-969. doi: 10.1007/s40264-020-00962-z. Drug Saf. 2020. PMID: 32613595 Review.
Cationic arginine-rich peptides represent a novel class of peptides being developed as neuroprotective agents for stroke and other acute and chronic neurological disorders. As a group, cationic arginine-rich peptides have a diverse range of other biological properties incl …
Cationic arginine-rich peptides represent a novel class of peptides being developed as neuroprotective agents for stroke and other ac …
Lessons from Recent Advances in Ischemic Stroke Management and Targeting Kv2.1 for Neuroprotection.
Yeh CY, Schulien AJ, Molyneaux BJ, Aizenman E. Yeh CY, et al. Int J Mol Sci. 2020 Aug 25;21(17):6107. doi: 10.3390/ijms21176107. Int J Mol Sci. 2020. PMID: 32854248 Free PMC article. Review.
Achieving neuroprotection in ischemic stroke patients has been a multidecade medical challenge. Numerous clinical trials were discontinued in futility and many were terminated in response to deleterious treatment effects. ...We further summarize the results a …
Achieving neuroprotection in ischemic stroke patients has been a multidecade medical challenge. Numerous clinical trial …
Conjugation of Therapeutic PSD-95 Inhibitors to the Cell-Penetrating Peptide Tat Affects Blood-Brain Barrier Adherence, Uptake, and Permeation.
Kristensen M, Kucharz K, Felipe Alves Fernandes E, Strømgaard K, Schallburg Nielsen M, Cederberg Helms HC, Bach A, Ulrikkaholm Tofte-Hansen M, Irene Aldana Garcia B, Lauritzen M, Brodin B. Kristensen M, et al. Pharmaceutics. 2020 Jul 14;12(7):661. doi: 10.3390/pharmaceutics12070661. Pharmaceutics. 2020. PMID: 32674358 Free PMC article.
Novel stroke therapies are needed. Inhibition of the interaction between the postsynaptic density-95 (PSD-95)/disc large/ZO-1 (PDZ) domains of PSD-95 and the N-methyl-D-aspartate (NMDA) receptor has been suggested as a strategy for relieving neu …
Novel stroke therapies are needed. Inhibition of the interaction between the postsynaptic density-95 (PSD-95)/disc larg …
Activation of CaMKII and GluR1 by the PSD-95-GluN2B Coupling-Dependent Phosphorylation of GluN2B in the Spinal Cord in a Rat Model of Type-2 Diabetic Neuropathic Pain.
Zhu YB, Jia GL, Wang JW, Ye XY, Lu JH, Chen JL, Zhang MB, Xie CS, Shen YJ, Tao YX, Li J, Cao H. Zhu YB, et al. J Neuropathol Exp Neurol. 2020 Jul 1;79(7):800-808. doi: 10.1093/jnen/nlaa035. J Neuropathol Exp Neurol. 2020. PMID: 32386416
The intrathecal injection of Ro25-6981 (a specific antagonist of GluN2B) or Tat-NR2B9c (a mimetic peptide disrupting the interaction between PSD-95 and GluN2B) induced an antihyperalgesic effect and blocked the increased expression of Tyr1472-GluN2B, C …
The intrathecal injection of Ro25-6981 (a specific antagonist of GluN2B) or Tat-NR2B9c (a mimetic peptide disrupting the inter …
Hypothermia but not NMDA receptor antagonism protects against stroke induced by distal middle cerebral arterial occlusion in mice.
Liu CW, Liao KH, Tseng H, Wu CM, Chen HY, Lai TW. Liu CW, et al. PLoS One. 2020 Mar 3;15(3):e0229499. doi: 10.1371/journal.pone.0229499. eCollection 2020. PLoS One. 2020. PMID: 32126102 Free PMC article.
Excitotoxicity mediated by the N-methyl-D-aspartate receptor (NMDAR) is believed to be a primary mechanism of neuronal injury following stroke. Thus, many drugs and therapeutic peptides were developed to inhibit either the NMDAR at the cell surface or its downstream intrac …
Excitotoxicity mediated by the N-methyl-D-aspartate receptor (NMDAR) is believed to be a primary mechanism of neuronal injury following s …
Modeling rapid and selective capture of nNOS-PSD-95 uncouplers from Sanhuang Xiexin decoction by novel molecularly imprinted polymers based on metal-organic frameworks.
Pan L, Ding Y, Ni X, Wang CZ, Jiang B, Zhang Y, Jiang N, Tang Y, Chen L, Yuan CS. Pan L, et al. RSC Adv. 2020 Feb 21;10(13):7671-7681. doi: 10.1039/c9ra10537a. eCollection 2020 Feb 18. RSC Adv. 2020. PMID: 35492204 Free PMC article.
Novel and highly selective molecularly imprinted polymers based on the surface of metal-organic frameworks, NH(2)-MIL-101(Cr) (MIL@MIP(S)), were successfully fabricated to capture neuronal nitric oxide synthase-postsynaptic density protein-95 (nNOS-PSD-95) uncoupler …
Novel and highly selective molecularly imprinted polymers based on the surface of metal-organic frameworks, NH(2)-MIL-101(Cr) (MIL@MIP(S)), …
Treatment of secondary brain injury by perturbing postsynaptic density protein-95-NMDA receptor interaction after intracerebral hemorrhage in rats.
Wang Z, Chen Z, Yang J, Yang Z, Yin J, Duan X, Shen H, Li H, Wang Z, Chen G. Wang Z, et al. J Cereb Blood Flow Metab. 2019 Aug;39(8):1588-1601. doi: 10.1177/0271678X18762637. Epub 2018 Mar 7. J Cereb Blood Flow Metab. 2019. PMID: 29513122 Free PMC article.
In this study, we found that there were an increase in the formation of PSD95-NR2B-nNOS complex and a decrease in the formation of neurexin-1-neuroligin-1-PSD95 complex after ICH, and this was accompanied by increased neuronal death and degeneration, and behavior dysfunction. PSD …
In this study, we found that there were an increase in the formation of PSD95-NR2B-nNOS complex and a decrease in the formation of neurexin- …
Targeted delivery of polypeptide nanoparticle for treatment of traumatic brain injury.
Wu P, Zhao H, Gou X, Wu X, Zhang S, Deng G, Chen Q. Wu P, et al. Int J Nanomedicine. 2019 May 31;14:4059-4069. doi: 10.2147/IJN.S202353. eCollection 2019. Int J Nanomedicine. 2019. PMID: 31213815 Free PMC article.
Background and purpose: Traumatic brain injury (TBI) is a major disease without effective treatment. Recently, Tat-NR2B9c peptide emerged as a promising neuroprotective agent, but limited in clinical translation by it low brain penetrabil …
Background and purpose: Traumatic brain injury (TBI) is a major disease without effective treatment. Recently, …
Selectivity, efficacy and toxicity studies of UCCB01-144, a dimeric neuroprotective PSD-95 inhibitor.
Bach A, Clausen BH, Kristensen LK, Andersen MG, Ellman DG, Hansen PBL, Hasseldam H, Heitz M, Özcelik D, Tuck EJ, Kopanitsa MV, Grant SGN, Lykke-Hartmann K, Johansen FF, Lambertsen KL, Strømgaard K. Bach A, et al. Neuropharmacology. 2019 May 15;150:100-111. doi: 10.1016/j.neuropharm.2019.02.035. Epub 2019 Mar 2. Neuropharmacology. 2019. PMID: 30836092
We have previously developed UCCB01-144, a dimeric PSD-95 inhibitor, which binds PSD-95 with high affinity and is neuroprotective in experimental stroke. ...Furthermore, UCCB01-144 was neuroprotective in a transient stroke model in …
We have previously developed UCCB01-144, a dimeric PSD-95 inhibitor, which binds PSD-95 with high affinit …
Poly-Arginine Peptides R18 and R18D Improve Functional Outcomes After Endothelin-1-Induced Stroke in the Sprague Dawley Rat.
Meloni BP, South SM, Gill DA, Marriott AL, Déziel RA, Jacques A, Blacker DJ, Knuckey NW. Meloni BP, et al. J Neuropathol Exp Neurol. 2019 May 1;78(5):426-435. doi: 10.1093/jnen/nlz014. J Neuropathol Exp Neurol. 2019. PMID: 30888409
Functional recovery poststroke was assessed using multiple forelimb placing tests and horizontal ladder test, and NA-1 (TAT-NR2B9c), a neuroprotective currently in phase 3 clinical stroke trials, was used as a benchmark. ...Furthermore, R18 at doses of 300 an …
Functional recovery poststroke was assessed using multiple forelimb placing tests and horizontal ladder test, and NA-1 (TAT-NR2B9c …
Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats.
Zaric M, Drakulic D, Stojanovic IG, Mitrovic N, Grkovic I, Martinovic J. Zaric M, et al. Brain Res. 2018 Jun 1;1688:73-80. doi: 10.1016/j.brainres.2018.03.023. Epub 2018 Mar 22. Brain Res. 2018. PMID: 29577884
Regional-specific postischemic changes were detected on protein level i.e. signs of neuronal damage in CA1 area was accompanied with hippocampal vGluT1, NR1, NR2B enhancement and PSD-95 decrement, while histological changes observed in layer III were associated with …
Regional-specific postischemic changes were detected on protein level i.e. signs of neuronal damage in CA1 area was accompanied with hippoca …
N-methyl D-aspartate receptor subtype 2B antagonist, Ro 25-6981, attenuates neuropathic pain by inhibiting postsynaptic density 95 expression.
Huang LE, Guo SH, Thitiseranee L, Yang Y, Zhou YF, Yao YX. Huang LE, et al. Sci Rep. 2018 May 18;8(1):7848. doi: 10.1038/s41598-018-26209-7. Sci Rep. 2018. PMID: 29777135 Free PMC article.
We demonstrate that the expression levels of total PSD-95 and cAMP response element binding protein (CREB), as well as phosphorylated NR2B, PSD-95, and CREB, in the spinal dorsal horn, and the interaction of NR2B with PSD-95 were increase …
We demonstrate that the expression levels of total PSD-95 and cAMP response element binding protein (CREB), as well as phospho …
Novel surface imprinted magnetic mesoporous silica as artificial antibodies for efficient discovery and capture of candidate nNOS-PSD-95 uncouplers for stroke treatment.
Huang J , Sun C , Yao D , Wang CZ , Zhang L , Zhang Y , Chen L , Yuan CS . Huang J , et al. J Mater Chem B. 2018 Mar 14;6(10):1531-1542. doi: 10.1039/c7tb03044d. Epub 2018 Feb 27. J Mater Chem B. 2018. PMID: 32254217
In the search for novel efficient nNOS-PSD-95 (nitric oxide synthase-postsynaptic density protein-95) uncouplers from natural products for stroke treatment, highly selective surface molecular imprinted polymers based on sandwich structured magnetic mesoporous …
In the search for novel efficient nNOS-PSD-95 (nitric oxide synthase-postsynaptic density protein-95) uncouplers from natural …
[Efficient discovery and capturing of nNOS-PSD-95 uncouplers from Trifolium pratense].
He HL, Pan LL, Gu XL, Huang JJ, Sun CH, Tang YL, Chen LN. He HL, et al. Zhongguo Zhong Yao Za Zhi. 2018 Feb;43(4):748-754. doi: 10.19540/j.cnki.cjcmm.20171208.001. Zhongguo Zhong Yao Za Zhi. 2018. PMID: 29600650 Chinese.
Simultaneously, the MMIPs prepared previously were used as sorbents for dispersive magnetic solid phase extraction(DSPE) to capture and identify potential nNOS-PSD-95 uncouplers from extracts of Trifolium pratense and the the activities of the screened compounds wer …
Simultaneously, the MMIPs prepared previously were used as sorbents for dispersive magnetic solid phase extraction(DSPE) to capture and iden …
Dissociation of nNOS from PSD-95 promotes functional recovery after cerebral ischaemia in mice through reducing excessive tonic GABA release from reactive astrocytes.
Lin YH, Liang HY, Xu K, Ni HY, Dong J, Xiao H, Chang L, Wu HY, Li F, Zhu DY, Luo CX. Lin YH, et al. J Pathol. 2018 Feb;244(2):176-188. doi: 10.1002/path.4999. Epub 2017 Dec 29. J Pathol. 2018. PMID: 29053192
One potential drug target, the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 (PSD-95), is critical to acute ischaemic damage and neurogenesis. We show that nNOS-PSD-95 dissociation …
One potential drug target, the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 …
Effects of Dimeric PSD-95 Inhibition on Excitotoxic Cell Death and Outcome After Controlled Cortical Impact in Rats.
Sommer JB, Bach A, Malá H, Gynther M, Bjerre AS, Gram MG, Marschner L, Strømgaard K, Mogensen J, Pickering DS. Sommer JB, et al. Neurochem Res. 2017 Dec;42(12):3401-3413. doi: 10.1007/s11064-017-2381-y. Epub 2017 Aug 21. Neurochem Res. 2017. PMID: 28828633
Therapeutic effects of PSD-95 inhibition have been demonstrated in numerous studies of stroke; however only few studies have assessed the effects of PSD-95 inhibitors in traumatic brain injury (TBI). As …
Therapeutic effects of PSD-95 inhibition have been demonstrated in numerous studies of stroke; however only few …
Effects of the dimeric PSD-95 inhibitor UCCB01-144 on functional recovery after fimbria-fornix transection in rats.
Sommer JB, Bach A, Malá H, Strømgaard K, Mogensen J, Pickering DS. Sommer JB, et al. Pharmacol Biochem Behav. 2017 Oct;161:62-67. doi: 10.1016/j.pbb.2017.09.008. Epub 2017 Sep 21. Pharmacol Biochem Behav. 2017. PMID: 28943199
Pharmacological inhibition of PSD-95 is a promising therapeutic strategy in the treatment of stroke, and positive effects of monomeric and dimeric PSD-95 inhibitors have been reported in numerous studies. However, whether therapeutic effe …
Pharmacological inhibition of PSD-95 is a promising therapeutic strategy in the treatment of stroke, and positive effec …
Postsynaptic density 95 (PSD-95) serine 561 phosphorylation regulates a conformational switch and bidirectional dendritic spine structural plasticity.
Wu Q, Sun M, Bernard LP, Zhang H. Wu Q, et al. J Biol Chem. 2017 Sep 29;292(39):16150-16160. doi: 10.1074/jbc.M117.782490. Epub 2017 Aug 8. J Biol Chem. 2017. PMID: 28790172 Free PMC article.
Postsynaptic density 95 (PSD-95) is a major synaptic scaffolding protein that plays a key role in bidirectional synaptic plasticity, which is a process important for learning and memory. It is known that PSD-95 shows increased dynamics upon indu …
Postsynaptic density 95 (PSD-95) is a major synaptic scaffolding protein that plays a key role in bidirectional synaptic pl …
ZL006, a small molecule inhibitor of PSD-95/nNOS interaction, does not induce antidepressant-like effects in two genetically predisposed rat models of depression and control animals.
Tillmann S, Pereira VS, Liebenberg N, Christensen AK, Wegener G. Tillmann S, et al. PLoS One. 2017 Aug 3;12(8):e0182698. doi: 10.1371/journal.pone.0182698. eCollection 2017. PLoS One. 2017. PMID: 28771575 Free PMC article.
This disruption can be achieved using small molecule inhibitors such as ZL006, which has attracted attention as ischemic stroke therapy in rodents and has been proposed as a potential novel treatment for depression. ...
This disruption can be achieved using small molecule inhibitors such as ZL006, which has attracted attention as ischemic stroke …
PSD-95 uncoupling from NMDA receptors by Tat- N-dimer ameliorates neuronal depolarization in cortical spreading depression.
Kucharz K, Søndergaard Rasmussen I, Bach A, Strømgaard K, Lauritzen M. Kucharz K, et al. J Cereb Blood Flow Metab. 2017 May;37(5):1820-1828. doi: 10.1177/0271678X16645595. Epub 2016 Jan 1. J Cereb Blood Flow Metab. 2017. PMID: 27107027 Free PMC article.
Cortical spreading depression is associated with activation of NMDA receptors, which interact with the postsynaptic density protein 95 (PSD-95) that binds to nitric oxide synthase (nNOS). Here, we tested whether inhibition of the nNOS/PSD-95/NMDA recep …
Cortical spreading depression is associated with activation of NMDA receptors, which interact with the postsynaptic density protein 95 (P …
The Neuroprotective Peptide Poly-Arginine-12 (R12) Reduces Cell Surface Levels of NMDA NR2B Receptor Subunit in Cortical Neurons; Investigation into the Involvement of Endocytic Mechanisms.
MacDougall G, Anderton RS, Edwards AB, Knuckey NW, Meloni BP. MacDougall G, et al. J Mol Neurosci. 2017 Feb;61(2):235-246. doi: 10.1007/s12031-016-0861-1. Epub 2016 Nov 20. J Mol Neurosci. 2017. PMID: 27866326
We have previously reported that cationic poly-arginine and arginine-rich cell-penetrating peptides display high-level neuroprotection and reduce calcium influx following in vitro excitotoxicity, as well as reduce brain injury in animal stroke models. ...Using cell …
We have previously reported that cationic poly-arginine and arginine-rich cell-penetrating peptides display high-level neuroprotection …
In vitro and in vivo effects of a novel dimeric inhibitor of PSD-95 on excitotoxicity and functional recovery after experimental traumatic brain injury.
Sommer JB, Bach A, Malá H, Strømgaard K, Mogensen J, Pickering DS. Sommer JB, et al. Eur J Neurosci. 2017 Jan;45(2):238-248. doi: 10.1111/ejn.13483. Epub 2016 Dec 4. Eur J Neurosci. 2017. PMID: 27859797
PSD-95 inhibitors have been shown to be neuroprotective in stroke, but have only to a very limited extent been evaluated in the treatment of traumatic brain injury (TBI) that has pathophysiological mechanisms in common with …
PSD-95 inhibitors have been shown to be neuroprotective in stroke, but have only to a very limited extent been e …
Neuroprotective efficacy of poly-arginine R18 and NA-1 (TAT-NR2B9c) peptides following transient middle cerebral artery occlusion in the rat.
Milani D, Cross JL, Anderton RS, Blacker DJ, Knuckey NW, Meloni BP. Milani D, et al. Neurosci Res. 2017 Jan;114:9-15. doi: 10.1016/j.neures.2016.09.002. Epub 2016 Sep 14. Neurosci Res. 2017. PMID: 27639457 Free article.
This provides strong justification for the continuing development of R18 as a neuroprotective treatment for stroke....
This provides strong justification for the continuing development of R18 as a neuroprotective treatment for stroke....
ATP from synaptic terminals and astrocytes regulates NMDA receptors and synaptic plasticity through PSD-95 multi-protein complex.
Lalo U, Palygin O, Verkhratsky A, Grant SG, Pankratov Y. Lalo U, et al. Sci Rep. 2016 Sep 19;6:33609. doi: 10.1038/srep33609. Sci Rep. 2016. PMID: 27640997 Free PMC article.
An activation of P2X receptors in turn leads to down-regulation of postsynaptic NMDA receptors via Ca(2+)-dependent de-phosphorylation and interaction with PSD-95 multi-protein complex. Genetic deletion of the PSD-95 or P2X4 receptors obliterated ATP-m …
An activation of P2X receptors in turn leads to down-regulation of postsynaptic NMDA receptors via Ca(2+)-dependent de-phosphorylation and i …
NOS knockout or inhibition but not disrupting PSD-95-NOS interaction protect against ischemic brain damage.
Kleinschnitz C, Mencl S, Kleikers PWM, Schuhmann MK, López MG, Casas AI, Sürün B, Reif A, Schmidt HHHW. Kleinschnitz C, et al. J Cereb Blood Flow Metab. 2016 Sep;36(9):1508-12. doi: 10.1177/0271678X16657094. Epub 2016 Jun 28. J Cereb Blood Flow Metab. 2016. PMID: 27354091 Free PMC article.
Promising results have been reported in preclinical stroke target validation for pharmacological principles that disrupt the N-methyl-D-aspartate receptor-post-synaptic density protein-95-neuronal nitric oxide synthase complex. ...We confirm the deleterious role of NOS1 in …
Promising results have been reported in preclinical stroke target validation for pharmacological principles that disrupt the N-methyl …
Effects of the dimeric PSD-95 inhibitor UCCB01-144 in mouse models of pain, cognition and motor function.
Andreasen JT, Nasser A, Caballero-Puntiverio M, Sahlholt M, Bach A, Gynther M, Strømgaard K, Pickering DS. Andreasen JT, et al. Eur J Pharmacol. 2016 Jun 5;780:166-73. doi: 10.1016/j.ejphar.2016.03.045. Epub 2016 Mar 28. Eur J Pharmacol. 2016. PMID: 27032314
We recently reported that UCCB01-125, a dimeric PSD-95 inhibitor with limited blood-brain-barrier permeability, reduced mechanical hypersensitivity in the complete Freund's adjuvant (CFA) inflammatory pain model, without disrupting cognitive or motor function …
We recently reported that UCCB01-125, a dimeric PSD-95 inhibitor with limited blood-brain-barrier permeability, reduced …
PDZ1 inhibitor peptide protects neurons against ischemia via inhibiting GluK2-PSD-95-module-mediated Fas signaling pathway.
Yin XH, Yan JZ, Yang G, Chen L, Xu XF, Hong XP, Wu SL, Hou XY, Zhang G. Yin XH, et al. Brain Res. 2016 Apr 15;1637:64-70. doi: 10.1016/j.brainres.2016.02.019. Epub 2016 Feb 15. Brain Res. 2016. PMID: 26892027
Respecting the selective inhibition of peptides on protein-protein interactions, they might become potent methods in ischemic stroke therapy. In this study, we investigated the effect of PDZ1 inhibitor peptide on ischemic neuron apoptosis and the relative mec …
Respecting the selective inhibition of peptides on protein-protein interactions, they might become potent methods in ischemic stro …
A beacon of hope in stroke therapy-Blockade of pathologically activated cellular events in excitotoxic neuronal death as potential neuroprotective strategies.
Hoque A, Hossain MI, Ameen SS, Ang CS, Williamson N, Ng DC, Chueh AC, Roulston C, Cheng HC. Hoque A, et al. Pharmacol Ther. 2016 Apr;160:159-79. doi: 10.1016/j.pharmthera.2016.02.009. Epub 2016 Feb 17. Pharmacol Ther. 2016. PMID: 26899498 Review.
Excitotoxicity, a pathological process caused by over-stimulation of ionotropic glutamate receptors, is a major cause of neuronal loss in acute and chronic neurological conditions such as ischaemic stroke, Alzheimer's and Huntington's diseases. Effective neuroprotec …
Excitotoxicity, a pathological process caused by over-stimulation of ionotropic glutamate receptors, is a major cause of neuronal loss in ac …
Employment of Molecularly Imprinted Polymers to High-Throughput Screen nNOS-PSD-95 Interruptions: Structure and Dynamics Investigations on Monomer-Template Complexation.
Wang Y, Zhao T, Dai P, Jiang N, Li F. Wang Y, et al. Chemphyschem. 2016 Mar 16;17(6):893-901. doi: 10.1002/cphc.201500941. Epub 2016 Jan 20. Chemphyschem. 2016. PMID: 26728445
Molecularly imprinted polymers (MIPs) are employed to screen nNOS-PSD-95 (neuronal nitric oxide synthase post-synaptic density protein-95) interruptions. 5-(3,5-Dichloro-2-hydroxybenzylamino)-2-hydroxybenzoic acid (ZL006; a potential drug candidate for the treatment …
Molecularly imprinted polymers (MIPs) are employed to screen nNOS-PSD-95 (neuronal nitric oxide synthase post-synaptic density …
Ocular Dominance Plasticity after Stroke Was Preserved in PSD-95 Knockout Mice.
Greifzu F, Parthier D, Goetze B, Schlüter OM, Löwel S. Greifzu F, et al. PLoS One. 2016 Mar 1;11(3):e0149771. doi: 10.1371/journal.pone.0149771. eCollection 2016. PLoS One. 2016. PMID: 26930616 Free PMC article.
In fact, using intrinsic signal optical imaging, we show here that OD-plasticity was preserved in V1 of adult PSD-95 KO mice after an S1-lesion but not in PSD-95 wildtype (WT)-mice. ...The preserved OD-plasticity in the PSD-95 …
In fact, using intrinsic signal optical imaging, we show here that OD-plasticity was preserved in V1 of adult PSD-95 KO …
The R18 Polyarginine Peptide Is More Effective Than the TAT-NR2B9c (NA-1) Peptide When Administered 60 Minutes after Permanent Middle Cerebral Artery Occlusion in the Rat.
Milani D, Knuckey NW, Anderton RS, Cross JL, Meloni BP. Milani D, et al. Stroke Res Treat. 2016;2016:2372710. doi: 10.1155/2016/2372710. Epub 2016 May 10. Stroke Res Treat. 2016. PMID: 27247825 Free PMC article.
We examined the dose responsiveness of polyarginine R18 (100, 300, and 1000 nmol/kg) when administered 60 minutes after permanent middle cerebral artery occlusion (MCAO). The TAT-NR2B9c peptide, which is known to be neuroprotective in rodent and nonhuman primate …
We examined the dose responsiveness of polyarginine R18 (100, 300, and 1000 nmol/kg) when administered 60 minutes after permanent middle cer …
Small-molecule inhibitors at the PSD-95/nNOS interface protect against glutamate-induced neuronal atrophy in primary cortical neurons.
Doucet MV, O'Toole E, Connor T, Harkin A. Doucet MV, et al. Neuroscience. 2015 Aug 20;301:421-38. doi: 10.1016/j.neuroscience.2015.06.004. Epub 2015 Jun 10. Neuroscience. 2015. PMID: 26071957
Since the NMDA-R is functionally coupled to nNOS via the postsynaptic protein 95kDa (PSD-95), inhibitors of the PSD-95/nNOS interaction were tested for their ability to protect against glutamate-induced suppression in neurite outgrowth. ...These …
Since the NMDA-R is functionally coupled to nNOS via the postsynaptic protein 95kDa (PSD-95), inhibitors of the PSD …
Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions.
Bach A, Pedersen SW, Dorr LA, Vallon G, Ripoche I, Ducki S, Lian LY. Bach A, et al. Sci Rep. 2015 Jul 16;5:12157. doi: 10.1038/srep12157. Sci Rep. 2015. PMID: 26177569 Free PMC article.
ZL006 and IC87201 have been presented as efficient inhibitors of the nNOS/PSD-95 protein-protein interaction and shown great promise in cellular experiments and animal models of ischemic stroke and pain. ...Our data show that under the applied in vitro …
ZL006 and IC87201 have been presented as efficient inhibitors of the nNOS/PSD-95 protein-protein interaction and shown great p …
Delayed Administration of Tat-HA-NR2B9c Promotes Recovery After Stroke in Rats.
Zhou HH, Tang Y, Zhang XY, Luo CX, Gao LY, Wu HY, Chang L, Zhu DY. Zhou HH, et al. Stroke. 2015 May;46(5):1352-8. doi: 10.1161/STROKEAHA.115.008886. Epub 2015 Apr 7. Stroke. 2015. Retraction in: Stroke. 2020 Apr;51(4):e72. doi: 10.1161/STR.0000000000000224. PMID: 25851770 Retracted.
BACKGROUND AND PURPOSE: Previous studies reported that Tat-NR2B9c, a peptide disrupting the N-methyl-d-aspartate receptor-postsynaptic density protein-95 interaction, reduced ischemic damage in the acute phase after stroke. ...The aim of this study is …
BACKGROUND AND PURPOSE: Previous studies reported that Tat-NR2B9c, a peptide disrupting the N-methyl-d-aspartate receptor-post …
Tat-NR2B9c prevents excitotoxic neuronal superoxide production.
Chen Y, Brennan-Minnella AM, Sheth S, El-Benna J, Swanson RA. Chen Y, et al. J Cereb Blood Flow Metab. 2015 May;35(5):739-42. doi: 10.1038/jcbfm.2015.16. Epub 2015 Feb 11. J Cereb Blood Flow Metab. 2015. PMID: 25669908 Free PMC article.
The Tat-NR2B9c peptide has shown clinical efficacy as a neuroprotective agent in acute stroke. Tat-NR2B9c is designed to prevent nitric oxide (NO) production by preventing postsynaptic density protein 95 (PSD-95) binding to N-methy …
The Tat-NR2B9c peptide has shown clinical efficacy as a neuroprotective agent in acute stroke. Tat-NR2B9c …
Design, synthesis, and characterization of fatty acid derivatives of a dimeric peptide-based postsynaptic density-95 (PSD-95) inhibitor.
Nissen KB, Andersen JJ, Haugaard-Kedström LM, Bach A, Strømgaard K. Nissen KB, et al. J Med Chem. 2015 Feb 12;58(3):1575-80. doi: 10.1021/jm501755d. Epub 2015 Jan 30. J Med Chem. 2015. PMID: 25590984
Dimeric peptide-based inhibitors of postsynaptic density-95 (PSD-95) can reduce ischemic brain damage and inflammatory pain in rodents. To modify the pharmacokinetic profile, we designed a series of fatty acid linked dimeric ligands, which potently inhibits …
Dimeric peptide-based inhibitors of postsynaptic density-95 (PSD-95) can reduce ischemic brain damage and inflammatory …
Interaction of nNOS with PSD-95 negatively controls regenerative repair after stroke.
Luo CX, Lin YH, Qian XD, Tang Y, Zhou HH, Jin X, Ni HY, Zhang FY, Qin C, Li F, Zhang Y, Wu HY, Chang L, Zhu DY. Luo CX, et al. J Neurosci. 2014 Oct 1;34(40):13535-48. doi: 10.1523/JNEUROSCI.1305-14.2014. J Neurosci. 2014. PMID: 25274829 Free PMC article.
More importantly, blocking nNOS-PSD-95 binding during the recovery stage improves stroke outcome via the promotion of regenerative repair in rats. Histone deacetylase 2 in NSCs may mediate the role of nNOS-PSD-95 association. Thus, nNOS-PSD …
More importantly, blocking nNOS-PSD-95 binding during the recovery stage improves stroke outcome via the promotion of r …
Melatonin improves neuroplasticity by upregulating the growth-associated protein-43 (GAP-43) and NMDAR postsynaptic density-95 (PSD-95) proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to transient focal cerebral ischemia even during a long-term recovery period.
Juan WS, Huang SY, Chang CC, Hung YC, Lin YW, Chen TY, Lee AH, Lee AC, Wu TS, Lee EJ. Juan WS, et al. J Pineal Res. 2014 Mar;56(2):213-23. doi: 10.1111/jpi.12114. Epub 2014 Jan 13. J Pineal Res. 2014. PMID: 24350898
Recent evidence shows that the NMDAR postsynaptic density-95 (PSD-95), growth-associated protein-43 (GAP-43), and matrix metalloproteinase-9 (MMP-9) protein enhance neuroplasticity at the subacute stage of stroke. ...Together, melatonin upregulates GAP …
Recent evidence shows that the NMDAR postsynaptic density-95 (PSD-95), growth-associated protein-43 (GAP-43), and matrix metal …
Uncoupling PSD-95 interactions leads to rapid recovery of cortical function after focal stroke.
Srejic LR, Hutchison WD, Aarts MM. Srejic LR, et al. J Cereb Blood Flow Metab. 2013 Dec;33(12):1937-43. doi: 10.1038/jcbfm.2013.153. Epub 2013 Sep 11. J Cereb Blood Flow Metab. 2013. PMID: 24022623 Free PMC article.
Spontaneous and evoked field potentials (fEPs) were recorded in the deep layers of the cortex with a linear microelectrode array for 3 hours after focal stroke in anesthetized rats. Tat-NR2B9c peptide, which confers neuroprotection by uncoupling the …
Spontaneous and evoked field potentials (fEPs) were recorded in the deep layers of the cortex with a linear microelectrode array for 3 hours …
Postsynaptic density protein (PSD)-95 expression is markedly decreased in the hippocampal CA1 region after experimental ischemia-reperfusion injury.
Yan BC, Park JH, Ahn JH, Lee JC, Won MH, Kang IJ. Yan BC, et al. J Neurol Sci. 2013 Jul 15;330(1-2):111-6. doi: 10.1016/j.jns.2013.04.023. Epub 2013 May 16. J Neurol Sci. 2013. PMID: 23684672
In brief, PSD-95 immunoreactivity in the CA1 dendrites was markedly decreased at early time after ischemia-reperfusion. We suggest that decreased PSD-95 immunoreactivity in the ischemic CA1 region may lead to a deficit of postsynaptic …
In brief, PSD-95 immunoreactivity in the CA1 dendrites was markedly decreased at early time after ischemia-reperfusion. …
Calmodulin kinase IV-dependent CREB activation is required for neuroprotection via NMDA receptor-PSD95 disruption.
Bell KF, Bent RJ, Meese-Tamuri S, Ali A, Forder JP, Aarts MM. Bell KF, et al. J Neurochem. 2013 Jul;126(2):274-87. doi: 10.1111/jnc.12176. Epub 2013 Mar 3. J Neurochem. 2013. PMID: 23363435 Free article.
We have previously shown that blocking NMDAR- post-synaptic density-95 (PSD95) interactions provides significant protection from excitotoxicity and in vivo ischaemia; however, the mechanism of neuroprotection is unclear. Here, we report that blocking PSD-9 …
We have previously shown that blocking NMDAR- post-synaptic density-95 (PSD95) interactions provides significant protection from excitotoxic …
UCCB01-125, a dimeric inhibitor of PSD-95, reduces inflammatory pain without disrupting cognitive or motor performance: comparison with the NMDA receptor antagonist MK-801.
Andreasen JT, Bach A, Gynther M, Nasser A, Mogensen J, Strømgaard K, Pickering DS. Andreasen JT, et al. Neuropharmacology. 2013 Apr;67:193-200. doi: 10.1016/j.neuropharm.2012.11.006. Epub 2012 Nov 20. Neuropharmacology. 2013. PMID: 23178182
Here, we compared the effects of a dimeric PSD-95 inhibitor, UCCB01-125, and the NMDAR antagonist, MK-801, on mechanical hypersensitivity in the complete Freund's adjuvant (CFA) model of inflammatory pain. ...By contrast, even high doses of UCCB01-125 were de …
Here, we compared the effects of a dimeric PSD-95 inhibitor, UCCB01-125, and the NMDAR antagonist, MK-801, on mechanica …
P38 MAPK is involved in enhanced NMDA receptor-dependent excitotoxicity in YAC transgenic mouse model of Huntington disease.
Fan J, Gladding CM, Wang L, Zhang LY, Kaufman AM, Milnerwood AJ, Raymond LA. Fan J, et al. Neurobiol Dis. 2012 Mar;45(3):999-1009. doi: 10.1016/j.nbd.2011.12.019. Epub 2011 Dec 14. Neurobiol Dis. 2012. PMID: 22198502
Previous studies have shown enhanced N-methyl-d-aspartate (NMDA)-induced excitotoxicity in neuronal models of HD, mediated in part by increased NMDA receptor (NMDAR) GluN2B subunit binding with the postsynaptic density protein-95 (PSD-95). In cultured hippocampal ne …
Previous studies have shown enhanced N-methyl-d-aspartate (NMDA)-induced excitotoxicity in neuronal models of HD, mediated in part by increa …
A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage.
Bach A, Clausen BH, Møller M, Vestergaard B, Chi CN, Round A, Sørensen PL, Nissen KB, Kastrup JS, Gajhede M, Jemth P, Kristensen AS, Lundström P, Lambertsen KL, Strømgaard K. Bach A, et al. Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3317-22. doi: 10.1073/pnas.1113761109. Epub 2012 Feb 17. Proc Natl Acad Sci U S A. 2012. PMID: 22343531 Free PMC article.
Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-D-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain dam …
Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuron …
The PSD-95/nNOS complex: new drugs for depression?
Doucet MV, Harkin A, Dev KK. Doucet MV, et al. Pharmacol Ther. 2012 Feb;133(2):218-29. doi: 10.1016/j.pharmthera.2011.11.005. Epub 2011 Nov 23. Pharmacol Ther. 2012. PMID: 22133842 Review.
In recent years, the NMDA receptor has emerged as a promising target for treating CNS disorders including stroke, pain and depression. In this review, we outline the molecular mechanisms underlying NMDA receptor signalling in neurons and in particular provide an overview o …
In recent years, the NMDA receptor has emerged as a promising target for treating CNS disorders including stroke, pain and depression …
Perturbing PSD-95 interactions with NR2B-subtype receptors attenuates spinal nociceptive plasticity and neuropathic pain.
D'Mello R, Marchand F, Pezet S, McMahon SB, Dickenson AH. D'Mello R, et al. Mol Ther. 2011 Oct;19(10):1780-92. doi: 10.1038/mt.2011.42. Epub 2011 Mar 22. Mol Ther. 2011. PMID: 21427709 Free PMC article.
Here, we show that spinal delivery of the mimetic peptide Tat-NR2B9c disrupts the interaction between PSD-95 and NR2B subunits in the dorsal horn and selectively reduces NMDA receptor-dependent events including wind-up of spinal sensory neurons, and bo …
Here, we show that spinal delivery of the mimetic peptide Tat-NR2B9c disrupts the interaction between PSD-95 and …
PSD-95-like membrane associated guanylate kinases (PSD-MAGUKs) and synaptic plasticity.
Xu W. Xu W. Curr Opin Neurobiol. 2011 Apr;21(2):306-12. doi: 10.1016/j.conb.2011.03.001. Epub 2011 Mar 28. Curr Opin Neurobiol. 2011. PMID: 21450454 Free PMC article. Review.
Overwhelming data have shown that PSD-95-like membrane associated guanylate kinases (PSD-MAGUKs), a major family of scaffold proteins at glutamatergic synapses, regulate basal synaptic AMPAR function and trafficking. It is now clear that PSD-MAGUKs have multifaceted …
Overwhelming data have shown that PSD-95-like membrane associated guanylate kinases (PSD-MAGUKs), a major family of scaffold p …
Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95.
Zhou L, Li F, Xu HB, Luo CX, Wu HY, Zhu MM, Lu W, Ji X, Zhou QG, Zhu DY. Zhou L, et al. Nat Med. 2010 Dec;16(12):1439-43. doi: 10.1038/nm.2245. Epub 2010 Nov 21. Nat Med. 2010. PMID: 21102461
Here we show that cerebral ischemia induces the interaction of nNOS with postsynaptic density protein-95 (PSD-95). ...Given the mechanism of nNOS-PSD-95 interaction, we developed a series of compounds and discovered a small-molecular inhibitor o …
Here we show that cerebral ischemia induces the interaction of nNOS with postsynaptic density protein-95 (PSD-95). ...G …
N-methyl-D-aspartate receptor subunit- and neuronal-type dependence of excitotoxic signaling through post-synaptic density 95.
Fan J, Vasuta OC, Zhang LY, Wang L, George A, Raymond LA. Fan J, et al. J Neurochem. 2010 Nov;115(4):1045-56. doi: 10.1111/j.1471-4159.2010.06994.x. Epub 2010 Sep 28. J Neurochem. 2010. PMID: 20831617 Free article.
However, it is not known if this PSD-95-dependent pathway contributes to excitotoxicity in other brain regions. It is also unclear whether the neuroprotective effects of Tat-NR2B9c, a membrane-permeant peptide that disrupts PSD-95/NMDAR b …
However, it is not known if this PSD-95-dependent pathway contributes to excitotoxicity in other brain regions. It is also unc …
Transduced PDZ1 domain of PSD-95 decreases Src phosphorylation and increases nNOS (Ser847) phosphorylation contributing to neuroprotection after cerebral ischemia.
Wang WW, Hu SQ, Li C, Zhou C, Qi SH, Zhang GY. Wang WW, et al. Brain Res. 2010 Apr 30;1328:162-70. doi: 10.1016/j.brainres.2010.02.055. Epub 2010 Mar 1. Brain Res. 2010. PMID: 20197063
Over-activation of NMDA receptor has been widely believed to be the main signal resulting in ischemic cell injury. We recently reported that the triplicate complex NR2A-PSD-95-Src is a signaling module to facilitate NMDA receptor over-activation. In addition, …
Over-activation of NMDA receptor has been widely believed to be the main signal resulting in ischemic cell injury. We recently report …
Overexpression of the PDZ1 domain of PSD-95 diminishes ischemic brain injury via inhibition of the GluR6.PSD-95.MLK3 pathway.
Hu SQ, Zhu J, Pei DS, Zong YY, Yan JZ, Hou XY, Zhang GY. Hu SQ, et al. J Neurosci Res. 2009 Dec;87(16):3626-38. doi: 10.1002/jnr.22163. J Neurosci Res. 2009. PMID: 19610093
Here, we first report that overexpression of the PDZ1 domain of PSD-95 protein exerts a protective role against neuronal death induced by cerebral ischemia-reperfusion in vivo and can prevent neuronal cell death induced by oxygen-glucose deprivation. Further …
Here, we first report that overexpression of the PDZ1 domain of PSD-95 protein exerts a protective role against neuronal death …
Interaction of postsynaptic density protein-95 with NMDA receptors influences excitotoxicity in the yeast artificial chromosome mouse model of Huntington's disease.
Fan J, Cowan CM, Zhang LY, Hayden MR, Raymond LA. Fan J, et al. J Neurosci. 2009 Sep 2;29(35):10928-38. doi: 10.1523/JNEUROSCI.2491-09.2009. J Neurosci. 2009. PMID: 19726651 Free PMC article.
We show that htt coimmunoprecipitated with SAP102 in HEK293T cells and striatal tissue from wild-type and YAC transgenic mice; however, the association of SAP102 with htt or the NMDAR NR2B subunit was unaffected by htt polyQ length, whereas association of PSD-95 wit …
We show that htt coimmunoprecipitated with SAP102 in HEK293T cells and striatal tissue from wild-type and YAC transgenic mice; however, the …
Neuroprotection after status epilepticus by targeting protein interactions with postsynaptic density protein 95.
Dykstra CM, Ratnam M, Gurd JW. Dykstra CM, et al. J Neuropathol Exp Neurol. 2009 Jul;68(7):823-31. doi: 10.1097/NEN.0b013e3181ac6b70. J Neuropathol Exp Neurol. 2009. PMID: 19535989
We examined the ability of Tat-NR2B9c to provide neuroprotection in the hippocampus of rats after 60 minutes of SE induced by the repeated injection of low doses of pilocarpine (10 mg/kg). Tat-NR2B9c was administered 3hours after the termination …
We examined the ability of Tat-NR2B9c to provide neuroprotection in the hippocampus of rats after 60 minutes of SE indu …
Inhibiting pro-death NMDA receptor signaling dependent on the NR2 PDZ ligand may not affect synaptic function or synaptic NMDA receptor signaling to gene expression.
Martel MA, Soriano FX, Baxter P, Rickman C, Duncan R, Wyllie DJ, Hardingham GE. Martel MA, et al. Channels (Austin). 2009 Jan-Feb;3(1):12-5. doi: 10.4161/chan.3.1.7864. Epub 2009 Jan 16. Channels (Austin). 2009. PMID: 19221512 Free article.
A peptide mimetic of the NR2B PDZ ligand (TAT-NR2B9c) reduces p38-mediated death in vitro and p38-dependent ischemic damage in vivo. In the absence of the PDZ ligand-p38 pathway, such as in TAT-NR2B9c-treated neurons, or in NMDAR-expressing non- …
A peptide mimetic of the NR2B PDZ ligand (TAT-NR2B9c) reduces p38-mediated death in vitro and p38-dependent ischemic da …
Increased tyrosine phosphorylation of PSD-95 by Src family kinases after brain ischaemia.
Du CP, Gao J, Tai JM, Liu Y, Qi J, Wang W, Hou XY. Du CP, et al. Biochem J. 2009 Jan 1;417(1):277-85. doi: 10.1042/BJ20080004. Biochem J. 2009. PMID: 18721130
As shown with a rabbit polyclonal antibody against phospho-PSD-95 (Tyr(523)), Tyr(523) phosphorylation is responsible for the increased tyrosine phosphorylation of PSD-95 induced by ischaemia in the rat hippocampus. In cultured hippocampal neuro …
As shown with a rabbit polyclonal antibody against phospho-PSD-95 (Tyr(523)), Tyr(523) phosphorylation is responsible for the …
Opposing effects of PSD-93 and PSD-95 on long-term potentiation and spike timing-dependent plasticity.
Carlisle HJ, Fink AE, Grant SG, O'Dell TJ. Carlisle HJ, et al. J Physiol. 2008 Dec 15;586(24):5885-900. doi: 10.1113/jphysiol.2008.163469. Epub 2008 Oct 20. J Physiol. 2008. PMID: 18936077 Free PMC article.
The membrane-associated guanylate kinases (MAGUKs) PSD-95, PSD-93 and SAP102 are thought to have crucial roles in both AMPA receptor trafficking and formation of NMDA receptor-associated signalling complexes involved in synaptic plasticity. While PSD- …
The membrane-associated guanylate kinases (MAGUKs) PSD-95, PSD-93 and SAP102 are thought to have crucial roles in both AMPA re …
Destabilization of the postsynaptic density by PSD-95 serine 73 phosphorylation inhibits spine growth and synaptic plasticity.
Steiner P, Higley MJ, Xu W, Czervionke BL, Malenka RC, Sabatini BL. Steiner P, et al. Neuron. 2008 Dec 10;60(5):788-802. doi: 10.1016/j.neuron.2008.10.014. Neuron. 2008. PMID: 19081375 Free PMC article.
N-terminal PDZ and C-terminal guanylate kinase domains of PSD-95 are required for both processes, indicating that PSD-95 coordinates multiple signals to regulate morphological plasticity. ...We propose that PSD-95 and CaMKII act at …
N-terminal PDZ and C-terminal guanylate kinase domains of PSD-95 are required for both processes, indicating that PSD- …
Excitotoxicity and focal cerebral ischemia induce truncation of the NR2A and NR2B subunits of the NMDA receptor and cleavage of the scaffolding protein PSD-95.
Gascón S, Sobrado M, Roda JM, Rodríguez-Peña A, Díaz-Guerra M. Gascón S, et al. Mol Psychiatry. 2008 Jan;13(1):99-114. doi: 10.1038/sj.mp.4002017. Epub 2007 May 8. Mol Psychiatry. 2008. PMID: 17486105
Although promising results are beginning to be obtained in the treatment of dementias, clinical trials with NMDAR antagonists for stroke, trauma and neurodegenerative disorders, such as Hungtinton's disease, have failed before. ...In this study, we report the rapid and ext …
Although promising results are beginning to be obtained in the treatment of dementias, clinical trials with NMDAR antagonists for stroke …
Preconditioning ischemia attenuates increased neurexin-neuroligin1-PSD-95 interaction after transient cerebral ischemia in rat hippocampus.
Li C, Han D, Zhang F, Zhou C, Yu HM, Zhang GY. Li C, et al. Neurosci Lett. 2007 Oct 22;426(3):192-7. doi: 10.1016/j.neulet.2007.08.065. Epub 2007 Sep 11. Neurosci Lett. 2007. PMID: 17904739
Our data show that preconditioning ischemia can down-regulate the increased neurexin-neuroligin1-PSD-95 interaction induced by ischemia injury and exerts a neuroprotective effect. Pre-treatment of N-methyl-D-aspartate (NMDA) receptor antagonist ketamin …
Our data show that preconditioning ischemia can down-regulate the increased neurexin-neuroligin1-PSD-95 interaction ind …
Crosstalk between PSD-95 and JIP1-mediated signaling modules: the mechanism of MLK3 activation in cerebral ischemia.
Zhang QX, Pei DS, Guan QH, Sun YF, Liu XM, Zhang GY. Zhang QX, et al. Biochemistry. 2007 Apr 3;46(13):4006-16. doi: 10.1021/bi0615386. Epub 2007 Mar 10. Biochemistry. 2007. PMID: 17348686
Here, we show that JIP1 maintains MLK3 in an inactive and monomeric state; once activated, MLK3 binds to PSD-95 and then dimerizes and autophosphorylates. In addition, a GluR6 C-terminus-containing peptide (Tat-GluR6-9c) and antisense oligonucleotides (AS-ODNs) agai …
Here, we show that JIP1 maintains MLK3 in an inactive and monomeric state; once activated, MLK3 binds to PSD-95 and then dimer …
Activation of c-Jun NH2-terminal kinase 3 is mediated by the GluR6.PSD-95.MLK3 signaling module following cerebral ischemia in rat hippocampus.
Tian H, Zhang QG, Zhu GX, Pei DS, Guan QH, Zhang GY. Tian H, et al. Brain Res. 2005 Nov 2;1061(1):57-66. doi: 10.1016/j.brainres.2005.09.001. Brain Res. 2005. PMID: 16256962
MLK3 subsequently activates c-Jun NH(2)-terminal kinase (JNK) via MAP kinase kinases (MKKs). We investigated the association of PSD-95 with GluR6 and MLK3, MLK3 autophosphorylation, the interaction of MLK3 with JNK3, and JNK3 phosphorylation following cerebral is …
MLK3 subsequently activates c-Jun NH(2)-terminal kinase (JNK) via MAP kinase kinases (MKKs). We investigated the association of PSD- …
Postsynaptic density protein 95 antisense oligodeoxynucleotides inhibits the activation of MLK3 and JNK3 via the GluR6.PSD-95.MLK3 signaling module after transient cerebral ischemia in rat hippocampus.
Pei DS, Sun YF, Guan QH, Hao ZB, Xu TL, Zhang GY. Pei DS, et al. Neurosci Lett. 2004 Aug 26;367(1):71-5. doi: 10.1016/j.neulet.2004.05.082. Neurosci Lett. 2004. PMID: 15308300
In this study, we investigated the effect of PSD-95 antisense oligodeoxynucleotides on the phosphorylation of MLK3, JNK3 and interactions of MLK3 and PSD-95 with kainate receptor (GluR6) by immunoprecipitation and immunoblotting. Transient (15 min) bra …
In this study, we investigated the effect of PSD-95 antisense oligodeoxynucleotides on the phosphorylation of MLK3, JNK3 and i …
Lithium suppressed Tyr-402 phosphorylation of proline-rich tyrosine kinase (Pyk2) and interactions of Pyk2 and PSD-95 with NR2A in rat hippocampus following cerebral ischemia.
Ma J, Zhang GY, Liu Y, Yan JZ, Hao ZB. Ma J, et al. Neurosci Res. 2004 Aug;49(4):357-62. doi: 10.1016/j.neures.2004.04.004. Neurosci Res. 2004. PMID: 15236860
In this study, we examined the time-course and the effect of lithium on Tyr-402 phosphorylation of Pyk2 and Tyr-416 phosphorylation of Src as well as the association of Pyk2 and NMDA receptor subunit 2A (NR2A) mediated by postsynaptic density protein 95 kDa (PSD-95) …
In this study, we examined the time-course and the effect of lithium on Tyr-402 phosphorylation of Pyk2 and Tyr-416 phosphorylation of Src a …
PSD-95 promotes CaMKII-catalyzed serine phosphorylation of the synaptic RAS-GTPase activating protein SynGAP after transient brain ischemia in rat hippocampus.
Song B, Yan XB, Zhang GY. Song B, et al. Brain Res. 2004 Apr 16;1005(1-2):44-50. doi: 10.1016/j.brainres.2004.01.032. Brain Res. 2004. PMID: 15044063
Recent studies have indicated that cerebral ischemia induces rapid serine phosphorylation of synaptic RAS-GTPase activating protein (SynGAP) by calcium/Camodulin-dependent protein kinase II (CaMKII) in rat hippocampus. ...Transient brain ischemia was induced by the …
Recent studies have indicated that cerebral ischemia induces rapid serine phosphorylation of synaptic RAS-GTPase activating protein ( …
Identification of PSD-95 as a regulator of dopamine-mediated synaptic and behavioral plasticity.
Yao WD, Gainetdinov RR, Arbuckle MI, Sotnikova TD, Cyr M, Beaulieu JM, Torres GE, Grant SG, Caron MG. Yao WD, et al. Neuron. 2004 Feb 19;41(4):625-38. doi: 10.1016/s0896-6273(04)00048-0. Neuron. 2004. PMID: 14980210 Free article.
At the synaptic level, enhanced long-term potentiation (LTP) of the frontocortico-accumbal glutamatergic synapses correlates with PSD-95 reduction in every case. Finally, targeted deletion of PSD-95 in an independent line of mice enhances LTP, augments …
At the synaptic level, enhanced long-term potentiation (LTP) of the frontocortico-accumbal glutamatergic synapses correlates with PSD …
Flavonoids from Radix Scutellariae as potential stroke therapeutic agents by targeting the second postsynaptic density 95 (PSD-95)/disc large/zonula occludens-1 (PDZ) domain of PSD-95.
Tang W, Sun X, Fang JS, Zhang M, Sucher NJ. Tang W, et al. Phytomedicine. 2004;11(4):277-84. doi: 10.1078/0944711041495173. Phytomedicine. 2004. PMID: 15185839
Excessive activation of N-methyl-D-aspartate receptors (NMDARs) and subsequent production of nitric oxide by neuronal nitric oxide synthase (nNOS) contribute to neuronal damage resulting from hypoxic and ischemic insults. NMDARs and nNOS are coupled together at the postsyn …
Excessive activation of N-methyl-D-aspartate receptors (NMDARs) and subsequent production of nitric oxide by neuronal nitric oxide synthase …
Lithium reduced N-methyl-D-aspartate receptor subunit 2A tyrosine phosphorylation and its interactions with Src and Fyn mediated by PSD-95 in rat hippocampus following cerebral ischemia.
Ma J, Zhang GY. Ma J, et al. Neurosci Lett. 2003 Sep 18;348(3):185-9. doi: 10.1016/s0304-3940(03)00784-5. Neurosci Lett. 2003. PMID: 12932824
After abdominal injection of LiCl (2 mg/kg) for 7 days, the data showed that together with the significant decrease in I/R-induced tyrosine phosphorylation of NR2A, the interactions of NR2A with Src and Fyn mediated by PSD-95 were also decreased significantly. Howev …
After abdominal injection of LiCl (2 mg/kg) for 7 days, the data showed that together with the significant decrease in I/R-induced tyrosine …
Increased tyrosine phosphorylation of alpha(1C) subunits of L-type voltage-gated calcium channels and interactions among Src/Fyn, PSD-95 and alpha(1C) in rat hippocampus after transient brain ischemia.
Hou XY, Zhang GY, Yan JZ, Liu Y. Hou XY, et al. Brain Res. 2003 Jul 25;979(1-2):43-50. doi: 10.1016/s0006-8993(03)02845-2. Brain Res. 2003. PMID: 12850569
More interestingly, co-immunoprecipitation analysis showed that 15 min of reperfusion dramatically increased the interaction between PSD-95 and alpha(1C) and promoted the formation of alpha(1C)-PSD-95-Src complexes, for the first time. The protein leve …
More interestingly, co-immunoprecipitation analysis showed that 15 min of reperfusion dramatically increased the interaction between PSD …
Tyrosine kinase and tyrosine phosphatase participate in regulation of interactions of NMDA receptor subunit 2A with Src and Fyn mediated by PSD-95 after transient brain ischemia.
Chen M, Hou X, Zhang G. Chen M, et al. Neurosci Lett. 2003 Mar 13;339(1):29-32. doi: 10.1016/s0304-3940(02)01439-8. Neurosci Lett. 2003. PMID: 12618293
In this study, we investigated the effects of protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) on the tyrosine phosphorylation of N-methyl-D-aspartate receptor subunit 2A (NR2A) and the interactions among NR2A, postsynaptic density protein 95 (PSD-95 …
In this study, we investigated the effects of protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) on the tyrosine phosphory …
PSD-95 regulates synaptic transmission and plasticity in rat cerebral cortex.
Béïque JC, Andrade R. Béïque JC, et al. J Physiol. 2003 Feb 1;546(Pt 3):859-67. doi: 10.1113/jphysiol.2002.031369. J Physiol. 2003. PMID: 12563010 Free PMC article.
However, the precise functional role played by PSD-95 in regulating synaptic transmission and plasticity remains undefined. To address this issue, we have overexpressed PSD-95 in cortical pyramidal neurons in organotypic brain slices using parti …
However, the precise functional role played by PSD-95 in regulating synaptic transmission and plasticity remains undefi …
Altered interaction between PSD-95 and the NMDA receptor following transient global ischemia.
Takagi N, Logan R, Teves L, Wallace MC, Gurd JW. Takagi N, et al. J Neurochem. 2000 Jan;74(1):169-78. doi: 10.1046/j.1471-4159.2000.0740169.x. J Neurochem. 2000. PMID: 10617118 Free article.
We investigated the effects of transient cerebral ischemia on protein interactions involving PSD-95 and the NMDA receptor in the rat hippocampus. ...The results indicate that molecular interactions involving PSD-95 and the NMDA receptor are modi …
We investigated the effects of transient cerebral ischemia on protein interactions involving PSD-95 and the NMDA recept …