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缓解衰老、神经退行性疾病和代谢性疾病中的细胞能量应激,SIRT1作为一个具有治疗前景的关键节点

Relieving Cellular Energy Stress in Aging, Neurodegenerative, and Metabolic Diseases, SIRT1 as a Therapeutic and Promising Node.

作者信息

Fang Yang, Wang Xifeng, Yang Danying, Lu Yimei, Wei Gen, Yu Wen, Liu Xing, Zheng Qingcui, Ying Jun, Hua Fuzhou

机构信息

Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang, China.

出版信息

Front Aging Neurosci. 2021 Sep 20;13:738686. doi: 10.3389/fnagi.2021.738686. eCollection 2021.

Abstract

The intracellular energy state will alter under the influence of physiological or pathological stimuli. In response to this change, cells usually mobilize various molecules and their mechanisms to promote the stability of the intracellular energy status. Mitochondria are the main source of ATP. Previous studies have found that the function of mitochondria is impaired in aging, neurodegenerative diseases, and metabolic diseases, and the damaged mitochondria bring lower ATP production, which further worsens the progression of the disease. Silent information regulator-1 (SIRT1) is a multipotent molecule that participates in the regulation of important biological processes in cells, including cellular metabolism, cell senescence, and inflammation. In this review, we mainly discuss that promoting the expression and activity of SIRT1 contributes to alleviating the energy stress produced by physiological and pathological conditions. The review also discusses the mechanism of precise regulation of SIRT1 expression and activity in various dimensions. Finally, according to the characteristics of this mechanism in promoting the recovery of mitochondrial function, the relationship between current pharmacological preparations and aging, neurodegenerative diseases, metabolic diseases, and other diseases was analyzed.

摘要

细胞内能量状态会在生理或病理刺激的影响下发生改变。作为对这种变化的响应,细胞通常会调动各种分子及其机制来促进细胞内能量状态的稳定。线粒体是ATP的主要来源。先前的研究发现,线粒体功能在衰老、神经退行性疾病和代谢性疾病中受损,受损的线粒体导致ATP生成减少,这进一步加剧了疾病的进展。沉默信息调节因子1(SIRT1)是一种多能分子,参与细胞内重要生物学过程的调节,包括细胞代谢、细胞衰老和炎症。在本综述中,我们主要讨论促进SIRT1的表达和活性有助于减轻生理和病理状况产生的能量应激。本综述还从多个维度探讨了SIRT1表达和活性精确调控的机制。最后,根据该机制在促进线粒体功能恢复方面的特点,分析了当前药物制剂与衰老、神经退行性疾病、代谢性疾病及其他疾病之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4f1/8489683/100adb6cf623/fnagi-13-738686-g0001.jpg

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