Dernie Francesco
Merton College, University of Oxford, Oxford, OX1 4JD, United Kingdom.
Neurochem Int. 2020 Sep;138:104756. doi: 10.1016/j.neuint.2020.104756. Epub 2020 May 16.
Healthy mitochondria play an essential role in energy metabolism, but dysfunctional mitochondria can cause perturbations in cellular processes which can ultimately lead to cell death. The process which selectively removes and degrades dysfunctional mitochondria, mitophagy, protects against the accumulation of abnormal mitochondria and hence has a protective role in maintaining cell health. Increasing numbers of studies have linked defective mitophagy to a range of diseases, including Parkinson's disease (PD). Whilst current treatment strategies in PD can improve the classical motor symptoms of the disease, they are also associated with often severe side-effects, and generally do not tackle the underlying progressive neurodegeneration seen in the disease. The identification of novel treatment targets, such as mitophagy, are therefore of increasing interest in PD research. This review will begin by outlining the process of mitophagy, before examining evidence implicating mitophagy in both monogenic and sporadic forms of PD, drawing links between mitophagy and wider pathological processes such as protein accumulation and neuroinflammation. Finally, this review will examine the diverse strategies employed to promote mitophagy so far, discuss considerations arising from these studies, and present a framework for eventual assessment of mitophagy-promoting compounds and their viability as a treatment strategy for PD patients.
健康的线粒体在能量代谢中起着至关重要的作用，但功能失调的线粒体可导致细胞过程紊乱，最终导致细胞死亡。选择性清除和降解功能失调线粒体的过程，即线粒体自噬，可防止异常线粒体的积累，因此在维持细胞健康方面具有保护作用。越来越多的研究将有缺陷的线粒体自噬与一系列疾病联系起来，包括帕金森病（PD）。虽然目前PD的治疗策略可以改善该疾病的典型运动症状，但它们也常常伴有严重的副作用，并且通常无法解决该疾病中潜在的进行性神经退行性变问题。因此，识别新的治疗靶点，如线粒体自噬，在PD研究中越来越受到关注。本综述将首先概述线粒体自噬的过程，然后研究线粒体自噬与单基因和散发性PD相关的证据，阐述线粒体自噬与更广泛的病理过程（如蛋白质积累和神经炎症）之间的联系。最后，本综述将研究目前用于促进线粒体自噬的各种策略，讨论这些研究中出现的问题，并提出一个最终评估促进线粒体自噬化合物及其作为PD患者治疗策略可行性的框架。
