alpha-chymotrypsin has been researched along with Huntington-Disease* in 2 studies
2 other study(ies) available for alpha-chymotrypsin and Huntington-Disease
Article | Year |
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Inhibition of p38 Mitogen-Activated Protein Kinase Ameliorates HAP40 Depletion-Induced Toxicity and Proteasomal Defect in Huntington's Disease Model.
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by an expansion of polyglutamine stretch (polyQ) at the N-terminus of huntingtin (Htt) protein. The abnormally expanded polyQ stretch of mutant Htt makes it prone to aggregate, leading to neuropathology. HAP40 is a 40-kDa huntingtin-associated protein with undefined functions. HAP40 protein has been shown to increase in HD patients and HD mouse model cells. However, recent proteomic analysis provides new evidence that HAP40 protein is decreased in the striatum of HD knockin model mice. In this study, we developed HAP40-specific antibody and showed that both HAP40 mRNA and its encoded protein were reduced in HD striatal neuronal STHDH Topics: Animals; Autophagy; Cell Line; Chymotrypsin; Corpus Striatum; Disease Models, Animal; Green Fluorescent Proteins; Huntingtin Protein; Huntington Disease; Intracellular Signaling Peptides and Proteins; Mice; Mutant Proteins; p38 Mitogen-Activated Protein Kinases; Proteasome Endopeptidase Complex; Protein Aggregates; Protein Kinase Inhibitors; Protein Subunits; Solubility; Ubiquitin | 2021 |
Neuronal induction of the immunoproteasome in Huntington's disease.
Huntington's disease (HD) inclusions are stained with anti-ubiquitin and anti-proteasome antibodies. This, together with proteasome activity studies on transfected cells, suggest that an impairment of the ubiquitin-proteasome system (UPS) may be key in HD pathogenesis. To test whether proteasome activity is impaired in vivo, we performed enzymatic assays for the three peptidase activities of the proteasome in brain extracts from the HD94 conditional mouse model of HD. We found no inhibition of any of the activities, suggesting that if UPS impairment happens in vivo, it is not at the level of the proteasome catalytic core. Intriguingly, the chymotrypsin- and trypsin-like activities increased selectively in the affected and aggregate-containing regions: cortex and striatum. Western blot analysis revealed no difference in total proteasome content whereas an increase in the interferon-inducible subunits of the immunoproteasome, LMP2 and LMP7, was observed. These subunits confer to the proteasome catalytic properties that are optimal for MHC-I peptide presentation. Immunohistochemistry in control mouse brain revealed LMP2 and LMP7 mainly in neurons. Accordingly, their increase in HD94 mice predominantly took place in neurons, and 5% of the ubiquitin-positive cortical aggregates were also LMP2-positive. Ultrastructural analysis of neurons with high level of immunoproteasome subunits revealed signs of neurodegeneration like nuclear indentation or fragmentation and dark cell appearance. The neuronal induction of LMP2 and LMP7 and the associated signs of neurodegeneration were also found in HD postmortem brains. Our results indicate that LMP2 and LMP7 participate in normal neuronal physiology and suggest a role in HD neurodegeneration. Topics: Aged; Animals; Brain; Cerebral Cortex; Chymotrypsin; Cysteine Endopeptidases; Female; Humans; Huntington Disease; Immunohistochemistry; Male; Mice; Mice, Transgenic; Multienzyme Complexes; Neostriatum; Neurons; Proteasome Endopeptidase Complex; Trypsin; Ubiquitins | 2003 |