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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DOI：
10.1007/s12264-023-01056-3
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发表时间：
2023-04
影响因子：
5.6
通讯作者：
Yuping Hao;Lingzhan Shao;Jianan Hou;Yan Zhang;Yuqian Ma;Jinhao Liu;Chuan Xu;Fujun Chen;Li Cao;Y. Ping
中科院分区：
文献类型：
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作者：
Yuping Hao;Lingzhan Shao;Jianan Hou;Yan Zhang;Yuqian Ma;Jinhao Liu;Chuan Xu;Fujun Chen;Li Cao;Y. Ping
白藜芦醇（Resveratrol，RES）是一种天然的多酚类植物化学物质，通过激活去乙酰化酶1（Sirtuin 1，Sirt 1/Sir 2）而被认为是预防和治疗阿尔茨海默病（Alzheimer's disease，AD）的抗衰老分子。在这项研究中，我们测试了RES和Sirt 1/Sir 2对睡眠和求偶记忆的影响，在果蝇模型中过表达淀粉样前体蛋白（APP），其复制和突变导致家族性AD。我们发现，在APP果蝇中，RES补充17天后，果蝇Sir 2（dSir 2）的转录水平轻微但显著增加，但7天后则没有。RES和dSir 2几乎完全逆转了APP果蝇的睡眠和记忆缺陷。我们进一步证明了dSir 2在果蝇中起着睡眠促进剂的作用。有趣的是，RES在没有dSir 2 indSir 2-null突变体的情况下增加睡眠，并且RES在dSir 2过表达或敲除APP果蝇时进一步增强睡眠。最后，我们发现RES和dSir 2可能通过抑制果蝇β-分泌酶（dBACE）来减少APP果蝇中的Aβ聚集体。我们的数据表明，RES拯救APP诱导的行为缺陷和Aβ负担很大程度上，但不是唯一的，通过Sir 2。
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 aDrosophilamodel by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase ofDrosophila Sir2(dSir2) by RES supplementation for up to 17 days inAPPflies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits inAPPflies. We further demonstrated that dSir2 acts as a sleep promotor inDrosophilaneurons. Interestingly, RES increased sleep in the absence of dSir2 indSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down inAPPflies. Finally, we showed that Aβ aggregates inAPPflies were reduced by RES and dSir2, probablyviainhibitingDrosophilaβ-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively,viadSir2.