Sharma Bunty, Pal Deeksha, Sharma Ujjawal, Kumar Aman
Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), Mullana, Haryana, India.
Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Front Mol Neurosci. 2022 Jul 6;15:921908. doi: 10.3389/fnmol.2022.921908. eCollection 2022.
Mitochondria provide neurons not only energy as ATP to keep them growing, proliferating and developing, but they also control apoptosis. Due to their high bioenergetic demand, neurons which are highly specific terminally differentiated cells, essentially depend on mitochondria. Defective mitochondrial function is thus related to numerous age-linked neurodegenerative ailments like Alzheimer's disease (AD), in which the build-up of impaired and malfunctioning mitochondria has been identified as a primary sign, paying to disease development. Mitophagy, selective autophagy, is a key mitochondrial quality control system that helps neurons to stay healthy and functional by removing undesired and damaged mitochondria. Dysfunctional mitochondria and dysregulated mitophagy have been closely associated with the onset of ADs. Various proteins associated with mitophagy were found to be altered in AD. Therapeutic strategies focusing on the restoration of mitophagy capabilities could be utilized to strike the development of AD pathogenesis. We summarize the mechanism and role of mitophagy in the onset and advancement of AD, in the quality control mechanism of mitochondria, the consequences of dysfunctional mitophagy in AD, and potential therapeutic approaches involving mitophagy modulation in AD. To develop new therapeutic methods, a better knowledge of the function of mitophagy in the pathophysiology of AD is required.
线粒体不仅为神经元提供三磷酸腺苷（ATP）形式的能量，以维持其生长、增殖和发育，还控制细胞凋亡。由于神经元这种高度特异性的终末分化细胞对生物能量的需求很高，它们基本上依赖于线粒体。因此，线粒体功能缺陷与许多与年龄相关的神经退行性疾病有关，如阿尔茨海默病（AD），其中已确定受损和功能失调的线粒体积累是疾病发展的主要迹象。线粒体自噬，即选择性自噬，是一种关键的线粒体质量控制系统，通过清除不需要的和受损的线粒体来帮助神经元保持健康和功能正常。功能失调的线粒体和失调的线粒体自噬与AD的发病密切相关。在AD中发现，各种与线粒体自噬相关的蛋白质发生了改变。专注于恢复线粒体自噬能力的治疗策略可用于对抗AD发病机制的发展。我们总结了线粒体自噬在AD发病和进展中的机制和作用、在线粒体质量控制机制中的作用、AD中功能失调的线粒体自噬的后果以及涉及AD中线粒体自噬调节的潜在治疗方法。为了开发新的治疗方法，需要更好地了解线粒体自噬在AD病理生理学中的功能。
