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

IF 2.1 Q3 NEUROSCIENCES Journal of Huntington's disease Pub Date : 2024-01-01 DOI:10.3233/JHD-240028
Yasmeen Alshehabi, Dale D O Martin
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Abstract

 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.

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亨廷顿氏病的保护性蛋白分解:揭示亨廷顿蛋白翻译后肉豆蔻酰化在自噬中的作用
亨廷顿氏病(Huntington's disease,HD)是一种破坏性神经退行性疾病,以运动功能受损和认知能力下降为特征,最终导致死亡。HD是由亨廷顿蛋白(HTT)N端区域的多聚谷氨酰胺扩增引起的,这与HTT周转率降低、HTT蛋白水解增加、HTT聚集增加以及随后的神经元死亡有关。在这篇综述中,我们探讨了阻断D586处HTT蛋白水解的保护作用机制,该作用已被证明能挽救HD小鼠模型中的HD表型。直到最近,这一机制仍不清楚。在此,我们将讨论阻断 HTT 在 D586 处的蛋白水解如何通过纠正自噬促进 HTT 的周转,并通过 HTT 在 G553 处的翻译后肉豆蔻酰化使 HTT 成为更好的自噬底物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.80
自引率
9.70%
发文量
60
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