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Updated: Jun 12, 2026
06:49
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Published on: December 17, 2021
Current understanding on the pathogenesis of polyglutamine diseases
Xiao-Hui He1, Fang Lin, Zheng-Hong Qin
1Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Soochow University School of Medicine, Suzhou 215123, China.
Neuroscience Bulletin
|May 27, 2010
Summary
Polyglutamine (polyQ) diseases stem from expanded CAG repeats, leading to protein misfolding and neurodegeneration. This review explores common pathogenic mechanisms, including protein conformational changes and impaired proteolysis, in these debilitating conditions.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Polyglutamine (polyQ) diseases are a class of neurodegenerative disorders characterized by the expansion of CAG trinucleotide repeats in specific genes.
- These expanded repeats lead to the production of proteins with abnormally long polyglutamine tracts, causing cellular dysfunction.
Purpose of the Study:
- To review the common pathogenic mechanisms underlying various polyglutamine diseases.
- To elucidate the relationship between protein misfolding, proteolysis, and selective neuronal death in these disorders.
Main Methods:
- This review synthesizes existing research on the molecular pathogenesis of polyglutamine diseases.
- Focuses on protein conformational changes, proteolysis, and gene expression patterns.
Main Results:
- Expanded polyQ tracts induce protein misfolding and conformational changes, impacting protein function.
- Decreased proteolysis correlates with the late onset of polyQ diseases.
- Widespread expression of disease-associated proteins contributes to selective neuronal vulnerability.
Conclusions:
- Understanding these shared pathogenic pathways is crucial for developing therapeutic strategies for polyglutamine diseases.
- Targeting protein misfolding, enhancing proteolysis, and addressing selective neuronal death are potential therapeutic avenues.
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