ORCID
- Evelina Valionyte: 0000-0001-5590-2990
- Shouqing Luo: 0000-0002-7998-3059
Abstract
Abstract Huntington’s disease (HD) is a neurodegenerative disorder caused by an expanded polyglutamine (polyQ) tract in the huntingtin (HTT) protein. Mutant HTT (mHTT) toxicity is caused by its aggregation/oligomerisation. The striatum is the most vulnerable region, although all brain regions undergo neuronal degeneration in the disease. Here we show that the levels of Bim, a BH3-only protein, are significantly increased in HD human post-mortem and HD mouse striata, correlating with neuronal death. Bim reduction ameliorates mHTT neurotoxicity in HD cells. In the HD mouse model, heterozygous Bim knockout significantly mitigates mHTT accumulation and neuronal death, ameliorating disease-associated phenotypes and lifespan. Therefore, Bim could contribute to the progression of HD.
DOI Link
Publication Date
2019-12-09
Publication Title
Human Molecular Genetics
ISSN
0964-6906
Acceptance Date
2019-11-11
Deposit Date
2024-06-04
Embargo Period
2020-12-08
Recommended Citation
Roberts, S., Evans, T., Yang, Y., Fu, Y., Button, R., Sipthorpe, R., Cowan, K., Valionyte, E., Anichtchik, O., Li, H., Lu, B., & Luo, S. (2019) 'Bim contributes to the progression of Huntington's disease-associated phenotypes', Human Molecular Genetics, . Available at: 10.1093/hmg/ddz275
