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阿尔茨海默病中 BACE1 的翻译后修饰。

Post-Translational Modifications of BACE1 in Alzheimer's Disease.

机构信息

Institute of Meterial Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137,China | School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.

Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu, Sichuan 610000,China.

出版信息

Curr Neuropharmacol. 2022;20(1):211-222. doi: 10.2174/1570159X19666210121163224.

Abstract

Beta-Amyloid Cleaving Enzyme1 (BACE1) is a monospecific enzyme for the key ratelimiting step in the synthesis of beta-amyloid(Aβ) from cleavage of amyloid precursor protein (APP), to form senile plaques and causes cognitive dysfunction in Alzheimer's disease (AD). Post-translation modifications of BACE1, such as acetylation, glycosylation, palmitoylation, phosphorylation, play a crucial role in the trafficking and maturation process of BACE1. The study of BACE1 is of great importance not only for understanding the formation of toxic Aβ but also for the development of an effective therapeutic target for the treatment of AD. This paper review recent advances in the studies about BACE1, with focuses being paid to the relationship of Aβ, BACE1 with posttranslational regulation of BACE1. In addition, we specially reviewed studies about the compounds that can be used to affect post-translational regulation of BACE1 or regulate BACE1 in the literature, which can be used for subsequent research on whether BACE1 is a post-translationally modified drug.

摘要

β-淀粉样肽裂解酶 1(BACE1)是淀粉样前体蛋白(APP)裂解为β-淀粉样肽(Aβ)过程中的关键限速酶,特异性切割 APP,形成老年斑,导致阿尔茨海默病(AD)认知功能障碍。BACE1 的翻译后修饰,如乙酰化、糖基化、棕榈酰化、磷酸化,在 BACE1 的运输和成熟过程中起着至关重要的作用。研究 BACE1 不仅对了解有毒 Aβ的形成具有重要意义,而且对开发有效的 AD 治疗靶点也具有重要意义。本文综述了近年来关于 BACE1 的研究进展,重点关注 Aβ、BACE1 与 BACE1 翻译后调控的关系。此外,我们还特别综述了文献中可用于影响 BACE1 翻译后调控或调节 BACE1 的化合物,可用于后续研究 BACE1 是否是一种翻译后修饰药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d65/9199555/df1725572b37/CN-20-211_F1.jpg

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