Suppression of MAPK11 or HIPK3 reduces mutant Huntingtin levels in Huntington's disease models.
作者： Meng Yu , Yuhua Fu , Yijian Liang , Haikun Song , Yao Yao
DOI: 10.1038/CR.2017.113
关键词:
摘要: Most neurodegenerative disorders are associated with accumulation of disease-relevant proteins. Among them, Huntington disease (HD) is particular interest because its monogenetic nature. HD mainly caused by cytotoxicity the defective protein encoded mutant Huntingtin gene (HTT). Thus, lowering HTT (mHTT) levels would be a promising treatment strategy for HD. Here we report two kinases HIPK3 and MAPK11 as positive modulators mHTT both in cells vivo. Both regulate via their kinase activities, suggesting that inhibiting these may have therapeutic values. Interestingly, effects on mHTT-dependent, providing feedback mechanism which enhances own level thus contributing to progression. Importantly, knockout significantly rescues behavioral phenotypes knockin mouse model. Collectively, our data reveal new entry points target-discovery approaches similar diseases.
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