Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Eur J Neurosci. 2021 May;53(9):2946-2959. doi: 10.1111/ejn.14699. Epub 2020 Feb 25.
The critical role of mitochondrial dysfunction in the pathological mechanisms of neurodegenerative disorders, particularly Parkinson's disease (PD), is well established. Compelling evidence indicates that Parkinson's proteins (e.g., α-synuclein, Parkin, PINK1, DJ-1, and LRRK2) are associated with mitochondrial dysfunction and oxidative stress in PD. Significantly, there is a possible central role of alpha-synuclein (α-Syn) in the occurrence of mitochondrial dysfunction and oxidative stress by the mediation of different signaling pathways. Also, tau, traditionally considered as the main component of neurofibrillary tangles, aggregates and amplifies the neurotoxic effects on mitochondria by interacting with α-Syn. Moreover, oxidative stress caused by mitochondrial dysfunction favors assembly of both α-Syn and tau and also plays a key role in the formation of protein aggregates. In this review, we provide an overview of the relationship between these two pathological proteins and mitochondrial dysfunction in PD, and also summarize the underlying mechanisms in the interplay of α-Syn aggregation and phosphorylated tau targeting the mitochondria, to find new strategies to prevent PD processing.
线粒体功能障碍在神经退行性疾病（尤其是帕金森病，PD）的病理机制中起着至关重要的作用，这一点已得到充分证实。有确凿的证据表明，帕金森蛋白（例如α-突触核蛋白、Parkin、PINK1、DJ-1 和 LRRK2）与 PD 中的线粒体功能障碍和氧化应激有关。值得注意的是，α-突触核蛋白（α-Syn）通过不同的信号通路介导，可能在线粒体功能障碍和氧化应激的发生中发挥核心作用。此外，tau 传统上被认为是神经原纤维缠结的主要成分，通过与 α-Syn 相互作用聚集并放大对线粒体的神经毒性作用。此外，线粒体功能障碍引起的氧化应激有利于 α-Syn 和 tau 的组装，并且在蛋白质聚集体的形成中也起着关键作用。在这篇综述中，我们概述了这两种病理蛋白与 PD 中线粒体功能障碍之间的关系，并总结了 α-Syn 聚集和磷酸化 tau 靶向线粒体相互作用的潜在机制，以寻找预防 PD 进展的新策略。
