Resveratrol and Sir2 Reverse Sleep and Memory Defects Induced by Amyloid Precursor Protein  

作　　者：Yuping Hao Lingzhan Shao Jianan Hou Yan Zhang Yuqian Ma Jinhao Liu Chuan Xu Fujun Chen Li-Hui Cao Yong Ping 

机构地区：[1]Bio-X Institutes,Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education),Shanghai Jiao Tong University,Shanghai 200240,China [2]School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China

出　　处：《Neuroscience Bulletin》2023年第7期1117-1130,共14页神经科学通报（英文版）

基　　金：funded by grants from the National Natural Science Foundation of China(81970999);the Shanghai Rising-Star Program(19QA1404900);the Innovation Program of the Shanghai Municipal Education Commission(2019-01-07-00-02-E00037).

摘　　要：Resveratrol(RES),a natural polyphenolic phytochemical,has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer’s disease(AD)by the activation of sirtuin 1(Sirt1/Sir2).In this study,we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein(APP),whose duplications and mutations cause familial AD.We found a mild but significant transcriptional increase of Drosophila Sir2(dSir2)by RES supplementation for up to 17 days in APP flies,but not for 7 days.RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies.We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons.Interestingly,RES increased sleep in the absence of dSir2 in dSir2-null mutants,and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies.Finally,we showed that Aβaggregates in APP flies were reduced by RES and dSir2,probably via inhibiting Drosophilaβ-secretase(dBACE).Our data suggest that RES rescues the APP-induced behavioral deficits and Aβburden largely,but not exclusively,via dSir2.

关 键 词：RESVERATROL SIR2 SLEEP Amyloid precursor protein Β-SECRETASE DROSOPHILA 

分 类 号：R749.16[医药卫生—神经病学与精神病学]