Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Level 17, Preclinical Building, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia.
Mol Neurobiol. 2020 Dec;57(12):5193-5207. doi: 10.1007/s12035-020-02083-1. Epub 2020 Aug 31.
In the human body, cell division and metabolism are expected to transpire uneventfully for approximately 25 years. Then, secondary metabolism and cell damage products accumulate, and ageing phenotypes are acquired, causing the progression of disease. Among these age-related diseases, neurodegenerative diseases have attracted considerable attention because of their irreversibility, the absence of effective treatment and their relationship with social and economic pressures. Mechanistic (formerly mammalian) target of rapamycin (mTOR), sirtuin (SIRT) and insulin/insulin growth factor 1 (IGF1) signalling pathways are among the most important pathways in ageing-associated conditions, such as neurodegeneration. These longevity-related pathways are associated with a diversity of various processes, including metabolism, cognition, stress reaction and brain plasticity. In this review, we discuss the roles of sirtuin and mTOR in ageing and neurodegeneration, with an emphasis on their regulation of autophagy, apoptosis and mitochondrial energy metabolism. The intervention of neurodegeneration using potential antioxidants, including vitamins, phytochemicals, resveratrol, herbals, curcumin, coenzyme Q10 and minerals, specifically aimed at retaining mitochondrial function in the treatment of Alzheimer's disease, Parkinson's disease and Huntington's disease is highlighted.
在人体中，细胞分裂和新陈代谢预计会在大约 25 年内平稳进行。然后，次生代谢和细胞损伤产物积累，获得衰老表型，导致疾病进展。在这些与年龄相关的疾病中，神经退行性疾病因其不可逆转、缺乏有效治疗以及与社会和经济压力的关系而引起了相当大的关注。机械性（原哺乳动物）雷帕霉素靶蛋白（mTOR）、沉默调节蛋白（SIRT）和胰岛素/胰岛素样生长因子 1（IGF1）信号通路是与神经退行性变等与衰老相关的疾病最相关的通路之一。这些与长寿相关的通路与各种不同的过程相关，包括代谢、认知、应激反应和大脑可塑性。在这篇综述中，我们讨论了 SIRT 和 mTOR 在衰老和神经退行性变中的作用，重点讨论了它们对自噬、细胞凋亡和线粒体能量代谢的调节。强调了使用潜在抗氧化剂（包括维生素、植物化学物质、白藜芦醇、草药、姜黄素、辅酶 Q10 和矿物质）干预神经退行性变，特别是针对保留线粒体功能，治疗阿尔茨海默病、帕金森病和亨廷顿病。
