亨廷顿蛋白
亨廷顿病
神经营养因子
亨廷顿蛋白
脑源性神经营养因子
生物
转录因子
神经科学
突变体
细胞生物学
内科学
基因
遗传学
疾病
医学
受体
作者
Chiara Zuccato,Andrea Ciammola,Dorotea Rigamonti,Blair R. Leavitt,Donato Goffredo,Luciano Conti,Marcy E. MacDonald,Robert M. Friedlander,Vincenzo Silani,Michael R. Hayden,Tõnis Timmusk,Simonetta Sipione,Elena Cattaneo
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2001-07-20
卷期号:293 (5529): 493-498
被引量:1223
标识
DOI:10.1126/science.1059581
摘要
Huntingtin is a 350-kilodalton protein of unknown function that is mutated in Huntington's disease (HD), a neurodegenerative disorder. The mutant protein is presumed to acquire a toxic gain of function that is detrimental to striatal neurons in the brain. However, loss of a beneficial activity of wild-type huntingtin may also cause the death of striatal neurons. Here we demonstrate that wild-type huntingtin up-regulates transcription of brain-derived neurotrophic factor (BDNF), a pro-survival factor produced by cortical neurons that is necessary for survival of striatal neurons in the brain. We show that this beneficial activity of huntingtin is lost when the protein becomes mutated, resulting in decreased production of cortical BDNF. This leads to insufficient neurotrophic support for striatal neurons, which then die. Restoring wild-type huntingtin activity and increasing BDNF production may be therapeutic approaches for treating HD.
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