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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 stroke
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 patien …
Nonarteritic central retinal artery occlusion (NA-CRAO) is a variant of acute ischemic stroke (AIS) and is a cause of sudden severe l …
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 May 8:JN-RM-2343-22. doi: 10.1523/JNEUROSCI.2343-22.2023. Online ahead of print. J Neurosci. 2023. PMID: 37160364
CRH induced a more significant increase in the firing rate of PVN-RVLM neurons and sympathoexcitatory response in SHRs than in WKY rats, an effect that was blocked by pre-application of NMDARs antagonist AP5 and PSD-95 inhibitor, Tat-N-dimer. Blocking …
CRH induced a more significant increase in the firing rate of PVN-RVLM neurons and sympathoexcitatory response in SHRs than in WKY rats, an …
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
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, …
Moreover, administration of ZL006, a small molecular inhibitor disrupting the interaction of nNOS and PSD-95 (20 mg.kg( …
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. ...There were no statistic …
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- …
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.
The last approach constitutes a breakthrough in the field, by extending the therapeutic window to 16-24 h after stroke onset and reducing stroke mortality. The combination of pharmacological brain-protective strategies with reperfusion is the future of str
The last approach constitutes a breakthrough in the field, by extending the therapeutic window to 16-24 h after stroke onset and redu …
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
Neurobehavioral outcomes and somatosensory evoked potentials (SSEPs) were examined before and 28 days after ischemia-reperfusion. Brain infarction was assessed using Nissl staining. Primary cortical neuron cultures were exposed to oxygen-glucose deprivation (OGD) and treat …
Neurobehavioral outcomes and somatosensory evoked potentials (SSEPs) were examined before and 28 days after ischemia-reperfusion. Brain
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.
We also included as controls, the well-characterised neuroprotective TAT-NR2B9c peptide and the widely used heparin reversal peptide, protamine. Degranulation assay based on beta-hexosaminidase release demonstrated that R18 and R18D did not induce significant mast c …
We also included as controls, the well-characterised neuroprotective TAT-NR2B9c peptide and the widely used heparin reversal p …
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
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. ...We also highlight how advanced brain
For over 40 years, attempts to develop treatments that protect neurons and other brain cells against the cellular and biochemical con …
PRIMED2 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 outcome for: 1 …
BACKGROUND: Clinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be …
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 …
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 …
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.
We discuss the use of ticagrelor and the promising novel category of factor XI inhibitors in the subacute phase after stroke. We offer our insights on combined rivaroxaban and antiplatelet therapy, PCSK-9 inhibitors, and other non-statin hypolipidemic agents, …
We discuss the use of ticagrelor and the promising novel category of factor XI inhibitors in the subacute phase after stroke. …
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 …
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.
A mouse model of edematous acute pancreatitis was induced with caerulein and lipopolysaccharide in C57BL/6 mice. Tat-N-dimer was injected to inhibit the PSD-95 activity separately, or simultaneously with SB203580, inhibitor of p38 MAPK phosphory …
A mouse model of edematous acute pancreatitis was induced with caerulein and lipopolysaccharide in C57BL/6 mice. Tat-N-dimer was inje …
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.
Methods: The nature and stability of PSD-95 calpain-fragments was analyzed using in vitro assays or excitotoxic conditions induced in rat primary neuronal cultures or a mouse model of stroke. ...Results: Calpain cleaves three interdomain linker regions in …
Methods: The nature and stability of PSD-95 calpain-fragments was analyzed using in vitro assays or excitotoxic conditions ind …
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. ...Overall, we demonstrate that fragment screening can successfull
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.
A similar increase in spine elimination after MD occurred if PSD-95 was knocked down in single PNs of layer 2/3. Thus, structural plasticity is dictated cell autonomously by PSD-95 in vivo in awake mice. Loss of PSD-95 preserves hallmark …
A similar increase in spine elimination after MD occurred if PSD-95 was knocked down in single PNs of layer 2/3. Thus, structu …
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. ...Some new developments raise renewed hope for neuroprotect …
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 available thus …
Achieving neuroprotection in ischemic stroke patients has been a multidecade medical challenge. Numerous clinical trials were discont …
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 …
Novel stroke therapies are needed. Inhibition of the interaction between the postsynaptic density-95 (PSD-95
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 dow …
Excitotoxicity mediated by the N-methyl-D-aspartate receptor (NMDAR) is believed to be a primary mechanism of neuronal injury followi …
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) un …
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. ...We synthesized Tat-NR2B9c loaded self-assembled activatable protein nanoparticles, termed TN-APNPs, and demonstrated that TN-APNPs enh …
Background and purpose: Traumatic brain injury (TBI) is a major disease without effective treatment. ...We synth …
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
Inhibition of postsynaptic density protein-95 (PSD-95) decouples N-methyl-d-aspartate (NMDA) receptor downstream signaling and results in neuroprotection after focal cerebral ischemia. We have previously developed UCCB01-144, a dimeric PSD-95
Inhibition of postsynaptic density protein-95 (PSD-95) decouples N-methyl-d-aspartate (NMDA) receptor downstream
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
Therefore, I/R-governed alteration of vesicular glutamate transporter 1 (vGluT1), synaptic NMDAR subunit composition, postsynaptic density protein 95 (PSD-95) and neuronal morphology alone or following DHEA treatment were examined. ...Under physiological cond …
Therefore, I/R-governed alteration of vesicular glutamate transporter 1 (vGluT1), synaptic NMDAR subunit composition, postsynaptic density p …
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 mes …
In the search for novel efficient nNOS-PSD-95 (nitric oxide synthase-postsynaptic density protein-95) uncouplers from n …
[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
We show that nNOS-PSD-95 dissociation induced by microinjection of a recombinant fusion protein, Tat-nNOS-N(1-133) , or systemic administration of a small-molecule, ZL006, from day 4 to day 10 after photothrombotic ischaemia in mice reduced excessive tonic …
We show that nNOS-PSD-95 dissociation induced by microinjection of a recombinant fusion protein, Tat-nNOS-N(1-133) , or …
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 therapeut …
Pharmacological inhibition of PSD-95 is a promising therapeutic strategy in the treatment of stroke, and positiv …
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 synapti …
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.
N-methyl-D-aspartate receptor (NMDA-R) antagonists and nitric oxide inhibitors have shown promising efficacy in depression but commonly induce adverse events. To circumvent these, a more indirect disruption of the nitric oxide synthase/postsynaptic density protein 95
N-methyl-D-aspartate receptor (NMDA-R) antagonists and nitric oxide inhibitors have shown promising efficacy in depression but common …
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
Cortical spreading depression is associated with activation of NMDA receptors, which interact with the postsynaptic density protein 95
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 t …
We have previously reported that cationic poly-arginine and arginine-rich cell-penetrating peptides display high-level neuroprotection and r …
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
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.
However, post-synaptic density protein-95 is also coupled to potentially neuroprotective mechanisms. As post-synaptic density protein-95 inhibitors may interfere with potentially neuroprotective mechanisms and sufficient validation has often been an issue in …
However, post-synaptic density protein-95 is also coupled to potentially neuroprotective mechanisms. As post-synaptic density protein …
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 f …
We recently reported that UCCB01-125, a dimeric PSD-95 inhibitor with limited blood-brain-barrier permeability, …
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
Results showed that PDZ1 inhibitor peptide, which significantly disrupted GluK2-PSD-95 interaction, efficiently protected neuron from ischemia/reperfusion-induced apoptosis. ...Based on our previous report that GluK2-PSD-95 pathway increased Fas …
Results showed that PDZ1 inhibitor peptide, which significantly disrupted GluK2-PSD-95 interaction, efficiently protect …
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.
These events, referred to as pathologically activated events, are potential targets for the development of neuroprotectant therapeutics. Inhibitors blocking some of the known pathologically activated cellular events have been proven to be effective in reducing stroke
These events, referred to as pathologically activated events, are potential targets for the development of neuroprotectant therapeutics. …
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 tr …
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 KO mice ind …
In fact, using intrinsic signal optical imaging, we show here that OD-plasticity was preserved in V1 of adult PSD-95 KO mice a …
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. Treatmen …
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 …
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. 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. ...CONCLUSIONS: Dissociating …
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 …
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. ...Subcutaneous administration in rats showed extended stability and sustained release of these ligands. This …
Dimeric peptide-based inhibitors of postsynaptic density-95 (PSD-95) can reduce ischemic brain damage and …
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. ...Relative to controls, melatonin-tre …
Recent evidence shows that the NMDAR postsynaptic density-95 (PSD-95), growth-associated protein-43 (GAP-43), and matri …
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 PSD
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
The PSD-95 immunoreactivity was shown as beaded structure in the MAP-2-immunoreactive dendrites. ...We suggest that decreased PSD-95 immunoreactivity in the ischemic CA1 region may lead to a deficit of postsynaptic plasticity in the brain....
The PSD-95 immunoreactivity was shown as beaded structure in the MAP-2-immunoreactive dendrites. ...We suggest that decreased …
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.
Here, we report that blocking PSD-95 interactions with the Tat-NR2B9c peptide enhances a Ca2+-dependent protective pathway converging on cAMP Response Element binding protein (CREB) activation. ...Tat-NR2B9c-dependent neuroprotection and …
Here, we report that blocking PSD-95 interactions with the Tat-NR2B9c peptide enhances a Ca2+-dependent protecti …
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
An alternative approach to modulate the NMDAR-related activity is to perturb the NMDAR/PSD-95/nNOS complex by targeting PSD-95, thereby decreasing NO production without interfering with the NMDAR ion channel function. Here, we compared the effects of a …
An alternative approach to modulate the NMDAR-related activity is to perturb the NMDAR/PSD-95/nNOS complex by targeting PSD
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 hippoca …
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
Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-9
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.
Synaptic glutamatergic receptors including AMPA receptors and NMDA receptors (AMPARs and NMDARs) are embedded in the postsynaptic density, a highly organized protein network. Overwhelming data have shown that PSD-95-like membrane associated guanylate kinases (PSD
Synaptic glutamatergic receptors including AMPA receptors and NMDA receptors (AMPARs and NMDARs) are embedded in the postsynaptic density, a …
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). Disrupting nNOS-PSD-95 interaction via overexpressing the N-terminal amino acid residues 1-133 of nNOS (nNOS-N(1-133)) prevented g …
Here we show that cerebral ischemia induces the interaction of nNOS with postsynaptic density protein-95 (PSD-95). Disr …
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.
It is also unclear whether the neuroprotective effects of Tat-NR2B9c, a membrane-permeant peptide that disrupts PSD-95/NMDAR binding, correlate with uncoupling NR2B- and/or NR2A-type NMDARs from PSD-95. In this study, we used cultured hip …
It is also unclear whether the neuroprotective effects of Tat-NR2B9c, a membrane-permeant peptide that disrupts PSD- …
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
Further studies show that overexpression of PDZ1 can perturb the interaction of GluR6 with PSD-95 and suppress the assembly of the GluR6.PSD-95.MLK3 signaling module and therefore inhibit JNK activation. ...Overall, the essential role of the PDZ …
Further studies show that overexpression of PDZ1 can perturb the interaction of GluR6 with PSD-95 and suppress the assembly of …
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.
Others have shown that membrane-associated guanylate kinases (MAGUKs), such as PSD-95 and SAP102, modulate NMDAR surface expression and excitotoxicity in hippocampal and cortical neurons and that htt interacts with PSD-95. ...Treatment of cultured MSNs …
Others have shown that membrane-associated guanylate kinases (MAGUKs), such as PSD-95 and SAP102, modulate NMDAR surface expre …
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
Tat-NR2B9c was designed to disrupt protein interactions involving postsynaptic density protein 95 in the NMDAR signaling complex while not interfering with function of the NMDAR ion channel. ...Tat-NR2B9c did not reduce cell loss in the posterio
Tat-NR2B9c was designed to disrupt protein interactions involving postsynaptic density protein 95 in the NMDAR signalin
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
NMDA receptors (NMDARs) mediate ischemic brain damage, in part through interactions of the PDZ ligand of NR2 subunits with the PDZ domain proteins PSD-95 and neuronal nitric oxide synthase located within the NMDAR signaling complex. ...Furthermore, TAT
NMDA receptors (NMDARs) mediate ischemic brain damage, in part through interactions of the PDZ ligand of NR2 subunits with the PDZ do …
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
The present study demonstrates that brain ischaemia and reperfusion increase the tyrosine phosphorylation of PSD-95 in the rat hippocampus. PP2, a specific inhibitor of SrcPTKs (Src family protein tyrosine kinases), prevents the ischaemia-induced incre …
The present study demonstrates that brain ischaemia and reperfusion increase the tyrosine phosphorylation of PSD-95 in …
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.
While PSD-95, PSD-93, and SAP102 appear to have similar roles in AMPA receptor trafficking, it is not known whether these MAGUKs also have functionally similar roles in synaptic plasticity. ...Moreover, in contrast to the facilitation of LTP induction and dis …
While PSD-95, PSD-93, and SAP102 appear to have similar roles in AMPA receptor trafficking, it is not known whether the …
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.
Signaling through PSD-95 is required for activity-dependent spine growth and trafficking of SHANK2. N-terminal PDZ and C-terminal guanylate kinase domains of PSD-95 are required for both processes, indicating that PSD-95 coordinates multi …
Signaling through PSD-95 is required for activity-dependent spine growth and trafficking of SHANK2. N-terminal PDZ and C-termi …
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
In this study, we report the rapid and extensive proteolytic processing of NR2A, together with the scaffolding protein postsynaptic density-95 (PSD-95), induced by excitotoxic stimulation of cortical neurons in vitro and by transient focal cerebral ischemia. …
In this study, we report the rapid and extensive proteolytic processing of NR2A, together with the scaffolding protein postsynaptic density- …
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 ketamine can d …
Our data show that preconditioning ischemia can down-regulate the increased neurexin-neuroligin1-PSD-95 interaction induced by …
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-ODN …
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
Kainate receptor glutamate receptor 6 (GluR6) binds to the postsynaptic density protein 95 (PSD-95), which in turn anchors mixed lineage kinase 3 (MLK3) via SH3 domain in rat brain tissue. ...Our results indicate that the GluR6.PSD-95.MLK …
Kainate receptor glutamate receptor 6 (GluR6) binds to the postsynaptic density protein 95 (PSD-95), which in turn anch …
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
Our data show that the antisense oligodeoxynucleotides could inhibit phosphorylation of MLK3 and JNK3 and decrease the interactions of MLK3 and PSD-95 with GluR6. These results indicate that PSD-95 plays an important role in the formation of the …
Our data show that the antisense oligodeoxynucleotides could inhibit phosphorylation of MLK3 and JNK3 and decrease the interactions o …
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- …
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
To further illustrate the mechanisms underlying these processes, we examined the effects of transient (15 min) brain ischemia followed by reperfusion (0, 30 min, 6 h, 1, 3 days) on serine phosphorylation of SynGAP and interactions involving SynGAP, postsynaptic density pro …
To further illustrate the mechanisms underlying these processes, we examined the effects of transient (15 min) brain ischemia followe …
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
NMDARs and nNOS are coupled together at the postsynaptic membrane through their interaction with postsynaptic density protein (PSD) 95 via PSD-95/disc large/zonula occludens-1 (PDZ) domains. We used NMR (nuclear magnetic resonance) spectroscopy to scre …
NMDARs and nNOS are coupled together at the postsynaptic membrane through their interaction with postsynaptic density protein (PSD) …
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
In this study, we evaluated the alterations in the tyrosine phosphorylation level of alpha(1C) and in the interactions involving Src/Fyn, alpha(1C) and PSD-95 in the hippocampus after transient (15 min) brain ischemia followed by various times of reperfusion …
In this study, we evaluated the alterations in the tyrosine phosphorylation level of alpha(1C) and in the interactions involving Src/Fyn, al …
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
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.
PSD-95 is one of the most abundant proteins found in the postsynaptic density of excitatory synapses. ...To address this issue, we have overexpressed PSD-95 in cortical pyramidal neurons in organotypic brain slices using particle-mediated gene t
PSD-95 is one of the most abundant proteins found in the postsynaptic density of excitatory synapses. ...To address this issue
beta 1-adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of beta 1-adrenergic receptor interaction with N-methyl-D-aspartate receptors.
Hu LA, Tang Y, Miller WE, Cong M, Lau AG, Lefkowitz RJ, Hall RA. Hu LA, et al. J Biol Chem. 2000 Dec 8;275(49):38659-66. doi: 10.1074/jbc.M005938200. J Biol Chem. 2000. PMID: 10995758 Free article.
The interaction between beta(1)AR and PSD-95 is mediated by the last few amino acids of the beta(1)AR, and mutation of the beta(1)AR carboxyl terminus eliminated the binding and disrupted the co-localization of the beta(1)AR and PSD-95 in cells. Agonis …
The interaction between beta(1)AR and PSD-95 is mediated by the last few amino acids of the beta(1)AR, and mutation of the bet …
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.
The postsynaptic protein PSD-95 binds to NMDA receptor subunits NR2A and NR2B and to signaling molecules such as neuronal nitric oxide synthase and p135synGAP. ...The results indicate that molecular interactions involving PSD-95 and the NMDA receptor a …
The postsynaptic protein PSD-95 binds to NMDA receptor subunits NR2A and NR2B and to signaling molecules such as neuronal nitr …