A Promising Strategy to Treat Neurodegenerative Diseases by SIRT3 Activation.
A Promising Strategy to Treat Neurodegenerative Diseases by SIRT3 Activation.
复制标题
激活SIRT3治疗神经退行性疾病的新策略
DOI：
10.3390/ijms24021615
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发表时间：
2023-01-13
影响因子：
5.6
通讯作者：
Pugazhenthi, Subbiah
中科院分区：
文献类型：
--
作者：
Tyagi, Alpna;Pugazhenthi, Subbiah
关键词：
SIRT3是主要的线粒体脱乙酰酶，调节包括代谢酶和呼吸链组分在内的线粒体蛋白质的功能。虽然SIRT3在外周组织中的功能已经很好地建立，但其下调在神经退行性疾病中的意义开始显现。SIRT3在脑能量代谢中起关键作用，并为神经元提供底物灵活性。它还促进燃料底物产生组织和燃料消耗组织之间的代谢偶联。SIRT3介导基于生活方式的改变（如卡路里限制和运动）的健康益处。SIRT3缺乏与代谢综合征（MetS）相关，代谢综合征是肥胖、糖尿病和心血管疾病等疾病的先决条件。单纯的阿尔茨海默病（AD）是罕见的，据报道，它与这些疾病在老龄化人口中共存。SIRT3下调导致线粒体功能障碍、神经炎症和炎症，可能是AD发病机制的触发因素。最近的研究还表明，SIRT3可能通过多种途径起作用，以减少AD大脑中的斑块形成。在这篇综述中，我们概述了SIRT3在脑生理学和病理学中的作用，并讨论了几种SIRT3的激活剂，这些激活剂可以被认为是治疗痴呆症的潜在治疗剂。
SIRT3, the primary mitochondrial deacetylase, regulates the functions of mitochondrial proteins including metabolic enzymes and respiratory chain components. Although SIRT3’s functions in peripheral tissues are well established, the significance of its downregulation in neurodegenerative diseases is beginning to emerge. SIRT3 plays a key role in brain energy metabolism and provides substrate flexibility to neurons. It also facilitates metabolic coupling between fuel substrate-producing tissues and fuel-consuming tissues. SIRT3 mediates the health benefits of lifestyle-based modifications such as calorie restriction and exercise. SIRT3 deficiency is associated with metabolic syndrome (MetS), a precondition for diseases including obesity, diabetes, and cardiovascular disease. The pure form of Alzheimer’s disease (AD) is rare, and it has been reported to coexist with these diseases in aging populations. SIRT3 downregulation leads to mitochondrial dysfunction, neuroinflammation, and inflammation, potentially triggering factors of AD pathogenesis. Recent studies have also suggested that SIRT3 may act through multiple pathways to reduce plaque formation in the AD brain. In this review, we give an overview of SIRT3’s roles in brain physiology and pathology and discuss several activators of SIRT3 that can be considered potential therapeutic agents for the treatment of dementia.
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