Sirtuin 1 在衰老和神经退行性疾病中的作用：分子视角

IF 12.5 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2024-10-17 DOI:10.1016/j.arr.2024.102545

Riya Thapa , Ehssan Moglad , Muhammad Afzal , Gaurav Gupta , Asif Ahmad Bhat , Waleed Hassan almalki , Imran Kazmi , Sami I. Alzarea , Kumud pant , Thakur Gurjeet Singh , Sachin Kumar Singh , Haider Ali

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引用次数: 0

摘要

Sirtuin 1（SIRT1）是一种依赖于 NAD+ 的去乙酰化酶，已成为与衰老和神经退行性疾病相关的细胞过程的关键调节因子。SIRT1 可调节各种信号通路，包括参与自噬、氧化应激和线粒体功能的信号通路，这些信号通路在神经退行性疾病的发病机制中至关重要。本综述探讨了 SIRT1 在几种神经退行性疾病中的治疗潜力，包括阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）和肌萎缩侧索硬化症（ALS）。临床前研究表明，白藜芦醇、SRT1720 和 SRT2104 等 SIRT1 激活剂可通过降低氧化应激、增强自噬通量和促进神经元存活来缓解疾病症状。目前正在进行的临床试验正在评估这些 SIRT1 激活剂的疗效，这为未来针对神经退行性疾病的 SIRT1 治疗策略带来了希望。这篇综述探讨了 SIRT1 在衰老和神经退行性疾病中的作用，尤其关注其分子机制、治疗潜力和临床应用。

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The role of sirtuin 1 in ageing and neurodegenerative disease: A molecular perspective

Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, has emerged as a key regulator of cellular processes linked to ageing and neurodegeneration. SIRT1 modulates various signalling pathways, including those involved in autophagy, oxidative stress, and mitochondrial function, which are critical in the pathogenesis of neurodegenerative diseases. This review explores the therapeutic potential of SIRT1 in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Preclinical studies have demonstrated that SIRT1 activators, such as resveratrol, SRT1720, and SRT2104, can alleviate disease symptoms by reducing oxidative stress, enhancing autophagic flux, and promoting neuronal survival. Ongoing clinical trials are evaluating the efficacy of these SIRT1 activators, providing hope for future therapeutic strategies targeting SIRT1 in neurodegenerative diseases. This review explores the role of SIRT1 in ageing and neurodegenerative diseases, with a particular focus on its molecular mechanisms, therapeutic potential, and clinical applications.

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来源期刊

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.