靶向调控SIRT1与阿尔茨海默病治疗  

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

作　　者：沈丽丽 孙会艳[2,3] 王洪权 SHEN Li-Li;SUN Hui-Yan;WANG Hong-Quan(Department of Neurology,The Affiliated Hospital of Chifeng University,Chifeng 024005,China;Chifeng University Health Science Center,Chifeng 024000,China;Key Laboratory of Human Genetic Diseases in Inner Mongolia,Chifeng 024000,China;Department of Neurology,Aerospace Center Hospital,Peking University Aerospace School of Clinical Medicine,Beijing 100049,China)

机构地区：[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

出　　处：《生理学报》2023年第1期99-107,共9页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China (No. 81260196, 81450036);the Natural Science Foundation of Inner Mongolia Autonomous Region (IMAR)(No. 2020MS08175, 2021MS08131, 2021LHMS08024);Science Foundation of Universities of IMAR (No. NJZY19218);Program for Young Talents of Science and Technology in Universities of IMAR (No. NJYT-17-B23);Science Foundation of Aerospace Medical Health Technology (AMHT)(No. 2020YK02, 2021YK05);Science Foundation of Aerospace Center Hospital (ASCH)(No. YN202104)。

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。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 diseasecentered perspective and provides an up-to-date overview of the SIRT1 modulators and their potential as effective therapeutics in AD.

关 键 词：阿尔茨海默病 去乙酰化酶 SIRT1 SIRT1激活剂 

分 类 号：R749.16[医药卫生—神经病学与精神病学]