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

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

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Resveratrol(RES),a natural polyphenolic phyto-chemical,has been suggested as a putative anti-aging mole-cule 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 signifi-cant 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 dem-onstrated 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 Aβ aggregates in APP flies were reduced by RES and dSir2,probably via inhibiting Drosophila β-secretase(dBACE).Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely,but not exclusively,via dSir2.

ResveratrolSir2SleepAmyloid precursor proteinβ-SecretaseDrosophila

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

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Bio-X Institutes,Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education),Shanghai Jiao Tong University,Shanghai 200240,China

School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China

Bloomington Stock Center for the fly stocks used in this studyNational Natural Science Foundation of ChinaShanghai Rising-Star ProgramInnovation Program of the Shanghai Municipal Education Commission

8197099919QA14049002019-01-07-00-02-E00037

2023

10.1007/s12264-023-01056-3

神经科学通报(英文版)
中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD
影响因子：0.741
ISSN：1673-7067
年,卷(期)：2023.39(7)
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