Xiao Bin, Kuruvilla Joshua, Tan Eng-King
Department of Neurology, National Neuroscience Institute, Singapore, Singapore.
Neuroscience Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore.
NPJ Parkinsons Dis. 2022 Oct 18;8(1):135. doi: 10.1038/s41531-022-00402-y.
Mitophagy impairment and oxidative stress are cardinal pathological hallmarks in Parkinson's disease (PD), a common age-related neurodegenerative condition. The specific interactions between mitophagy and reactive oxygen species (ROS) have attracted considerable attention even though their exact interplay in PD has not been fully elucidated. We highlight the interactions between ROS and mitophagy, with a focus on the signalling pathways downstream to ROS that triggers mitophagy and draw attention to potential therapeutic compounds that target these pathways in both experimental and clinical models. Identifying a combination of ROS inhibitors and mitophagy activators to provide a physiologic balance in this complex signalling pathways may lead to a more optimal outcome. Deciphering the exact temporal relationship between mitophagy and oxidative stress and their triggers early in the course of neurodegeneration can unravel mechanistic clues that potentially lead to the development of compounds for clinical drug trials focusing on prodromic PD or at-risk individuals.
线粒体自噬功能障碍和氧化应激是帕金森病(PD)的主要病理特征,PD是一种常见的与年龄相关的神经退行性疾病。尽管线粒体自噬与活性氧(ROS)在PD中的具体相互作用尚未完全阐明,但它们之间的特定相互作用已引起了相当大的关注。我们着重介绍ROS与线粒体自噬之间的相互作用,重点关注ROS下游触发线粒体自噬的信号通路,并提请注意在实验模型和临床模型中靶向这些通路的潜在治疗化合物。确定ROS抑制剂和线粒体自噬激活剂的组合,以在这一复杂信号通路中实现生理平衡,可能会带来更理想的结果。解读线粒体自噬与氧化应激之间的确切时间关系及其在神经退行性变早期的触发因素,可以揭示可能导致开发针对前驱期PD或高危个体的临床药物试验化合物的机制线索。