Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 23 (12), 8511-8515

Prolyl Oligopeptidase Inhibition Reduces PolyQ Aggregation and Improves Cell Viability in Cellular Model of Huntington's Disease

Affiliations

Prolyl Oligopeptidase Inhibition Reduces PolyQ Aggregation and Improves Cell Viability in Cellular Model of Huntington's Disease

Susanna Norrbacka et al. J Cell Mol Med.

Abstract

No abstract available

Keywords: autophagy; huntingtin; neurodegeneration; protein aggregation; protein processing.

Conflict of interest statement

The authors confirm that there are no conflicts of interest.

Figures

Figure 1
Figure 1
KYP‐2047 attenuates lactacystin‐induced toxicity in 103Q‐expressing HeLa cells. Wild‐type (A‐B)‐, 25Q (C‐D)‐ and 103Q (E‐F)‐expressing HeLa cells were exposed to increasing amounts of a proteasomal inhibitor, lactacystin (1 nmol/L to 100 µmol/L). About 100 µmol/L of lactacystin was particularly toxic for 103Q HeLa cells (E) in LDH assay and 1 µmol/L KYP‐2047 significantly decreased LDH release. About 100 µmol/L lactacystin was toxic for all cell lines but in 103Q HeLa, 1 µmol/L KYP‐2047 attenuated lactacystin toxicity (F).*P < .05, Student's t test (n of parallel samples = 3; n of individual experiments = 3)
Figure 2
Figure 2
PREP inhibition reduces 103Q aggregation in cells. 103Q cells showed clear aggregates instead of diffuse soluble staining after lactacystin exposure (A‐B), and simultaneous incubation with 1 µmol/L KYP‐2047 reduces cytosolic aggregates (C). Further analysis by Western blot showed significant decrease in insoluble GFP levels (HMW GFP) in 103Q cells while in 25Q cells showed no significant aggregation (D‐E). Beclin1 levels were not significantly increased by KYP‐2047 (F‐G) but LC3BII was significantly elevated in 103Q cells compared to control (I). *P < .05; **P < .01; ***P < .001, 1‐way ANOVA with Tukey post‐test (n of parallel samples = 2; n of individual experiments = 3)

Similar articles

See all similar articles

References

    1. Jimenez‐Sanchez M, Licitra F, Underwood BR, Rubinsztein DC. Huntington’s disease: mechanisms of pathogenesis and therapeutic strategies. Cold Spring Harb Perspect Med. 2017;7:a024240. - PMC - PubMed
    1. Tabrizi SJ, Ghosh R, Leavitt BR. Huntingtin lowering strategies for disease modification in Huntington’s disease. Neuron. 2019;101:801‐819. - PubMed
    1. Bar‐Yosef T, Damri O, Agam G. Dual role of autophagy in diseases of the central nervous system. Front Cell Neurosci. 2019;13:196‐196. - PMC - PubMed
    1. Galluzzi L, Bravo‐San Pedro JM, Levine B, Green DR, Kroemer G. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat Rev Drug Discov. 2017;16:487‐511. - PMC - PubMed
    1. Savolainen MH, Richie CT, Harvey BK, Männistö PT, Maguire‐Zeiss KA, Myöhänen TT. The beneficial effect of a prolyl oligopeptidase inhibitor, KYP‐2047, on alpha‐synuclein clearance and autophagy in A30P transgenic mouse. Neurobiol Dis. 2014;68C:1‐15. - PubMed

LinkOut - more resources

Feedback