School of Psychiatry, University of New South Wales, Prince of Wales Hospital, Sydney, New South Wales, Australia.
Curr Opin Psychiatry. 2012 May;25(3):226-30. doi: 10.1097/YCO.0b013e32835112c1.
Sirtuins are a family of enzymes highly conserved in evolution and involved in mechanisms known to promote healthy ageing and longevity. This review aims to discuss recent advances in understanding the role of sirtuins, in particular mammalian SIRT1, in promoting longevity and its potential molecular basis for neuroprotection against cognitive ageing and Alzheimer's disease pathology.
Accumulative increase in oxidative stress during ageing has been shown to decrease SIRT1 activity in catabolic tissue, possibly by direct inactivation by reactive oxygen. SIRT1 overexpression prevents oxidative stress-induced apoptosis and increases resistance to oxidative stress through regulation of the FOXO family of forkhead transcription factors. In addition, resveratrol strongly stimulates SIRT1 deacetylase activity in a dose-dependent manner by increasing its binding affinity to both the acetylated substrate and NAD(+). Recently, SIRT1 has been shown to affect amyloid production through its influence over the ADAM10 gene. Upregulation of SIRT1 can also induce the Notch pathway and inhibit mTOR signalling.
Recent studies have revealed some of the mechanisms and pathways that are associated with the neuroprotective effects of SIRT1.
沉默信息调节因子 2 相关酶（Sirtuins）是进化上高度保守的酶家族，参与已知的促进健康衰老和长寿的机制。本综述旨在讨论理解 Sirtuins，特别是哺乳动物 SIRT1 ，在促进长寿及其对认知衰老和阿尔茨海默病病理的神经保护的潜在分子基础方面的最新进展。
在衰老过程中，氧化应激的累积增加已被证明会降低分解代谢组织中的 SIRT1 活性，可能是通过活性氧直接失活。SIRT1 的过表达可通过调节 FOXO 家族叉头转录因子来防止氧化应激诱导的细胞凋亡，并增加对氧化应激的抵抗力。此外，白藜芦醇通过增加其与乙酰化底物和 NAD(+) 的结合亲和力，以剂量依赖的方式强烈刺激 SIRT1 脱乙酰酶活性。最近，SIRT1 已被证明通过其对 ADAM10 基因的影响来影响淀粉样蛋白的产生。SIRT1 的上调还可以诱导 Notch 途径并抑制 mTOR 信号通路。
最近的研究揭示了与 SIRT1 的神经保护作用相关的一些机制和途径。
