Biomedical Research Center, College of Medicine, Qatar University, Doha, 2713, Qatar.
Department of Biomedical Sciences, College of Health Sciences, Qatar University, Doha, 2713, Qatar.
Curr Neuropharmacol. 2023;21(5):1184-1201. doi: 10.2174/1570159X20666221012122855.
Neurodegenerative disorders include different neurological conditions that affect nerve cells, causing the progressive loss of their functions and ultimately leading to loss of mobility, coordination, and mental functioning. The molecular mechanisms underpinning neurodegenerative disease pathogenesis are still unclear. Nonetheless, there is experimental evidence to demonstrate that the perturbation of mitochondrial function and dynamics play an essential role. In this context, mitochondrial biogenesis, the growth, and division of preexisting mitochondria, by controlling mitochondria number, plays a vital role in maintaining proper mitochondrial mass and function, thus ensuring efficient synaptic activity and brain function. Mitochondrial biogenesis is tightly associated with the control of cell division and variations in energy demand in response to extracellular stimuli; therefore, it may represent a promising therapeutic target for developing new curative approaches to prevent or counteract neurodegenerative disorders. Accordingly, several inducers of mitochondrial biogenesis have been proposed as pharmacological targets for treating diverse central nervous system conditions. The naturally occurring polyphenol resveratrol has been shown to promote mitochondrial biogenesis in various tissues, including the nervous tissue, and an ever-growing number of studies highlight its neurotherapeutic potential. Besides preventing cognitive impairment and neurodegeneration through its antioxidant and anti-inflammatory properties, resveratrol has been shown to be able to enhance mitochondria biogenesis by acting on its main effectors, including PGC-1α, SIRT1, AMPK, ERRs, TERT, TFAM, NRF-1 and NRF-2. This review aims to present and discuss the current findings concerning the impact of resveratrol on the machinery and main effectors modulating mitochondrial biogenesis in the context of neurodegenerative diseases.
神经退行性疾病包括影响神经细胞的不同神经状况，导致其功能逐渐丧失，最终导致运动、协调和精神功能丧失。神经退行性疾病发病机制的分子机制尚不清楚。尽管如此，有实验证据表明，线粒体功能和动态的失调起着重要的作用。在这种情况下，线粒体生物发生，即通过控制线粒体数量来生长和分裂现有的线粒体，对于维持适当的线粒体质量和功能至关重要，从而确保有效的突触活动和大脑功能。线粒体生物发生与细胞分裂的控制和对外界刺激的能量需求变化密切相关；因此，它可能代表着开发新的治疗方法以预防或对抗神经退行性疾病的有前途的治疗靶点。因此，已经提出了几种线粒体生物发生的诱导剂作为治疗各种中枢神经系统疾病的药理学靶点。天然存在的多酚白藜芦醇已被证明可促进包括神经组织在内的各种组织中的线粒体生物发生，越来越多的研究强调了其神经治疗潜力。除了通过其抗氧化和抗炎特性预防认知障碍和神经退行性变外，白藜芦醇还被证明能够通过作用于其主要效应物，包括 PGC-1α、SIRT1、AMPK、ERRs、TERT、TFAM、NRF-1 和 NRF-2，来增强线粒体生物发生。本综述旨在介绍和讨论关于白藜芦醇在神经退行性疾病背景下对调节线粒体生物发生的机制和主要效应物的影响的最新发现。
