Bim contributes to the progression of Huntington's disease-associated phenotypes

Sheridan L. Roberts; Tracey Evans; Yi Yang; Yuhua Fu; Robert W. Button; Rebecca J. Sipthorpe; Katrina Cowan; Evelina Valionyte; Oleg Anichtchik; Huiliang Li; Boxun Lu; Shouqing Luo

doi:10.1093/hmg/ddz275

Bim contributes to the progression of Huntington's disease-associated phenotypes

Sheridan L. Roberts, Tracey Evans, Yi Yang, Yuhua Fu, Robert W. Button, Rebecca J. Sipthorpe, Katrina Cowan, Evelina Valionyte, Oleg Anichtchik, Huiliang Li, Boxun Lu, Shouqing Luo^*

^*Corresponding author for this work

Peninsula Medical School

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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.

Original language	English
Number of pages	0
Journal	Human Molecular Genetics
Volume	0
Issue number	0
Early online date	9 Dec 2019
DOIs	https://doi.org/10.1093/hmg/ddz275
Publication status	E-pub ahead of print - 9 Dec 2019

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title = "Bim contributes to the progression of Huntington's disease-associated phenotypes",

abstract = "Abstract Huntington{\textquoteright}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.",

author = "Roberts, {Sheridan L.} and Tracey Evans and Yi Yang and Yuhua Fu and Button, {Robert W.} and Sipthorpe, {Rebecca J.} and Katrina Cowan and Evelina Valionyte and Oleg Anichtchik and Huiliang Li and Boxun Lu and Shouqing Luo",

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T1 - Bim contributes to the progression of Huntington's disease-associated phenotypes

AU - Roberts, Sheridan L.

AU - Evans, Tracey

AU - Yang, Yi

AU - Fu, Yuhua

AU - Button, Robert W.

AU - Sipthorpe, Rebecca J.

AU - Cowan, Katrina

AU - Valionyte, Evelina

AU - Anichtchik, Oleg

AU - Li, Huiliang

AU - Lu, Boxun

AU - Luo, Shouqing

PY - 2019/12/9

Y1 - 2019/12/9

N2 - 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.

AB - 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.

U2 - 10.1093/hmg/ddz275

DO - 10.1093/hmg/ddz275

M3 - Article

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VL - 0

JO - Human Molecular Genetics

JF - Human Molecular Genetics

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Bim contributes to the progression of Huntington's disease-associated phenotypes

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