Protective Proteolysis in Huntington's Disease: Unraveling the Role of Post-Translational Myristoylation of Huntingtin in Autophagy

被引:0
|
作者
Alshehabi, Yasmeen [1 ]
Martin, Dale D. O. [1 ]
机构
[1] Univ Waterloo, Fac Sci, Dept Biol, NeurdyPhagy Lab, Waterloo, ON, Canada
基金
加拿大健康研究院; 加拿大自然科学与工程研究理事会;
关键词
Autophagy; huntingtin; myristoylation; neurodegeneration; proteolysis; N-TERMINAL FRAGMENTS; MUTANT HUNTINGTIN; CASPASE CLEAVAGE; TRINUCLEOTIDE REPEAT; BINDING PROTEIN; MOUSE MODEL; CAG REPEAT; TOXICITY; MINOCYCLINE; ACTIVATION;
D O I
10.3233/JHD-240028
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Huntington's disease (HD) is a devastating neurodegenerative disorder characterized by impaired motor function and cognitive decline, ultimately leading to death. HD is caused by a polyglutamine expansion in the N-terminal region of the huntingtin (HTT) protein, which is linked to decreased HTT turnover, increased HTT proteolysis, increased HTT aggregation, and subsequent neuronal death. In this review, we explore the mechanism of the protective effect of blocking HTT proteolysis at D586, which has been shown to rescue the HD phenotype in HD mouse models. Until recently, the mechanism remained unclear. Herein, we discuss how blocking HTT proteolysis at D586 promotes HTT turnover by correcting autophagy, and making HTT a better autophagy substrate, through post-translational myristoylation of HTT at G553.
引用
收藏
页码:267 / 277
页数:11
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