摘要
老龄化对老年人口的生活质量提出了重大挑战。由于神经元损伤导致认知障碍、运动不协调和行为不一致的风险在社会老龄化个体中相对较高。大脑通过其结构和功能的完整性来调节重要的生理事件;然而,大脑对衰老相关障碍的易感性预示着神经退行性疾病的发生。线粒体功能障碍会损害大脑中的生物能机制、突触可塑性和钙稳态,从而充分暗示线粒体是加速衰老相关神经变性的主要因果因素。我们回顾了线粒体在健康大脑中的基本功能,旨在通过提问来解决衰老相关疾病的关键问题:1) 衰老大脑中的线粒体出了什么问题? 2) 线粒体损伤对运动功能和精神症状有何影响? 3) 环境化学物质和代谢疾病如何影响线粒体功能?此外,我们分享了关于靶向线粒体以减缓衰老和相关神经退行性疾病进展的药物发现方法的机遇和陷阱的见解。
关键词: 线粒体、衰老、膜通透性、突触可塑性、神经精神症状、代谢发病率、生物标志物。
Current Drug Targets
Title:Aging of Brain Related with Mitochondrial Dysfunctions
Volume: 22 Issue: 14
关键词: 线粒体、衰老、膜通透性、突触可塑性、神经精神症状、代谢发病率、生物标志物。
摘要: Advancing age presents a major challenge for the elderly population in terms of quality of life. The risk of cognitive impairment, motor in-coordination, and behavioral inconsistency due to neuronal damage is relatively higher in aging individuals of society. The brain, through its structural and functional integrity, regulates vital physiological events; however, the susceptibility of the brain to aging-related disturbances signals the onset of neurodegenerative diseases. Mitochondrial dysfunctions impair bioenergetic mechanism, synaptic plasticity, and calcium homeostasis in the brain, thus sufficiently implying mitochondria as a prime causal factor in accelerating aging-related neurodegeneration. We have reviewed the fundamental functions of mitochondria in a healthy brain and aimed to address the key issues in aging-related diseases by asking: 1) What goes wrong with mitochondria in the aging brain? 2) What are the implications of mitochondrial damage on motor functions and psychiatric symptoms? 3) How environmental chemicals and metabolic morbidities affect mitochondrial functions? Further, we share insights on opportunities and pitfalls in drug discovery approaches targeting mitochondria to slow down the progression of aging and related neurodegenerative diseases.
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Aging of Brain Related with Mitochondrial Dysfunctions, Current Drug Targets 2021; 22 (14) . https://dx.doi.org/10.2174/1389450121999201209202247
DOI https://dx.doi.org/10.2174/1389450121999201209202247 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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