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沉默信息调节因子1/过氧化物酶体增殖物激活受体γ共激活因子-1α轴:帕金森病和阿尔茨海默病治疗的一个有前景的靶点。

Silent Information Regulator 1/Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α Axis: A Promising Target for Parkinson's and Alzheimer's Disease Therapies.

作者信息

Goyal Ahsas, Kumari Anshika, Verma Aanchal, Chaudhary Vandana, Agrawal Vaibhav, Yadav Harlokesh Narayan

机构信息

Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India.

All India Institute of Medical Sciences (AIIMS), New Delhi, India.

出版信息

J Biochem Mol Toxicol. 2024 Dec;38(12):e70078. doi: 10.1002/jbt.70078.

Abstract

One of the key challenges in medical research is developing safe medications to treat neurodegenerative disorders. Increased oxidative stress, mitochondrial dysfunction, and neuroinflammation are common features of Alzheimer's disease (AD) and Parkinson's disease (PD). Silent information regulator 1 (SIRT-1), part of the sirtuin family, plays a critical role in various physiological processes by binding to histones and nonhistone proteins. SIRT-1 primarily mitigates oxidative stress and regulates mitochondrial activity by maintaining the deacetylated form of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), ensuring stable PGC-1α levels. Research has shown reduced SIRT-1/PGC-1α expression in AD and PD models. Targeting this pathway presents a promising therapeutic approach for managing AD and PD, potentially leading to disease-modifying treatments and improved outcomes. This review highlights the findings of various studies suggesting that the SIRT-1/PGC-1α pathway promotes mitochondrial biogenesis, synaptic plasticity, and cognitive function, as well as exerts antioxidant, anti-inflammatory, and anti-apoptotic effects, offering a potential method for AD and PD treatment.

摘要

医学研究中的关键挑战之一是开发用于治疗神经退行性疾病的安全药物。氧化应激增加、线粒体功能障碍和神经炎症是阿尔茨海默病(AD)和帕金森病(PD)的常见特征。沉默信息调节因子1(SIRT-1)是沉默调节蛋白家族的一部分,通过与组蛋白和非组蛋白蛋白质结合,在各种生理过程中发挥关键作用。SIRT-1主要通过维持过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)的去乙酰化形式来减轻氧化应激并调节线粒体活性,确保PGC-1α水平稳定。研究表明,在AD和PD模型中,SIRT-1/PGC-1α表达降低。针对这一途径为管理AD和PD提供了一种有前景的治疗方法,可能会带来疾病修饰治疗并改善预后。本综述强调了各项研究的结果,这些结果表明SIRT-1/PGC-1α途径可促进线粒体生物合成、突触可塑性和认知功能,并具有抗氧化、抗炎和抗凋亡作用,为AD和PD治疗提供了一种潜在方法。

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