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靶向调控SIRT1与阿尔茨海默病治疗

沈丽丽¹, 孙会艳^2,3, 王洪权^4,*

¹赤峰学院附属医院神经内科，赤峰 024005；²赤峰学院医学部，赤峰 024000；³内蒙古人类遗传病研究重点实验室，赤峰 024000；⁴航天中心医院、北京大学航天临床医学院神经内科，北京 100049

摘要

沉默信息调节因子1 (silent information regulator 1, SIRT1)是哺乳动物NAD+依赖的去乙酰化酶沉默信息调节因子(sirtuin)家族的七种蛋白质之一。SIRT1具有神经保护作用，且研究揭示SIRT1在阿尔茨海默病(Alzheimer’s disease, AD)中具有潜在神经保护作用。SIRT1调节许多AD相关病理过程，包括调节淀粉样蛋白前体蛋白(amyloid-β precursor protein, APP)剪切、神经炎症、神经退行性变和线粒体功能障碍等。SIRT1在AD中受到了特别的关注，药理学或遗传学手段激活sirtuin通路在AD实验模型中显示出治疗作用。本综述阐述了SIRT1在AD中的病理作用机制最新研究进展，并对SIRT1诱导剂及其在AD中的治疗潜力进行了概述。

关键词： 阿尔茨海默病; 去乙酰化酶; SIRT1; SIRT1激活剂

Therapeutic potential of targeting SIRT1 for the treatment of Alzheimer’s disease

SHEN Li-Li¹, SUN Hui-Yan^2,3, WANG Hong-Quan^4,*

¹Department of Neurology, The Affiliated Hospital of Chifeng University, Chifeng 024005, China；²Chifeng University Health Science Center, Chifeng 024000, China；³Key Laboratory of Human Genetic Diseases in Inner Mongolia, Chifeng 024000, China；⁴Department of Neurology, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing 100049, China

Abstract

Silent information regulator 1 (SIRT1) is one of the seven mammalian proteins of the sirtuin family of NAD+-dependent deacetylases. SIRT1 plays a pivotal role in neuroprotection and ongoing research has uncovered a mechanism by which SIRT1 may exert a neuroprotective effect on Alzheimer’s disease (AD). Growing evidence demonstrates that SIRT1 regulates many pathological processes including amyloid-β precursor protein (APP) processing, neuroinflammation, neurodegeneration, and mitochondrial dysfunction. SIRT1 has recently received enormous attention, and pharmacological or transgenic approaches to activate the sirtuin pathway have shown promising results in the experimental models of AD. In the present review, we delineate the role of SIRT1 in AD from a disease- centered perspective and provides an up-to-date overview of the SIRT1 modulators and their potential as effective therapeutics in AD.

Key words: Alzheimer’s disease; deacetylases; SIRT1; SIRT1 activator

收稿日期：　　录用日期：

通讯作者：王洪权　　E-mail:

DOI: 10.13294/j.aps.2023.0007

引用本文：

沈丽丽, 孙会艳, 王洪权. 靶向调控SIRT1与阿尔茨海默病治疗[J]. 生理学报 2023; 75 (1): 99-107.

SHEN Li-Li, SUN Hui-Yan, WANG Hong-Quan. Therapeutic potential of targeting SIRT1 for the treatment of Alzheimer’s disease. Acta Physiol Sin 2023; 75 (1): 99-107 (in Chinese with English abstract).