Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Prog Brain Res. 2020;252:61-89. doi: 10.1016/bs.pbr.2020.02.005. Epub 2020 Mar 30.
Parkinson's disease (PD) is the second most common neurodegenerative disease, disabling millions worldwide. Despite the imperative PD poses, at present, there is no cure or means of slowing progression. This gap is attributable to our incomplete understanding of the factors driving pathogenesis. Research over the past several decades suggests that both cell-autonomous and non-cell autonomous processes contribute to the neuronal dysfunction underlying PD symptoms. The thesis of this review is that an intersection of these processes governs the pattern of pathology in PD. Studies of substantia nigra pars compacta (SNc) dopaminergic neurons, whose loss is responsible for the core motor symptoms of PD, suggest that they have a combination of traits-a long, highly branched axon, autonomous activity, and elevated mitochondrial oxidant stress-that predispose them to non-cell autonomous drivers of pathogenesis, like misfolded forms of alpha-synuclein (α-SYN) and inflammation. The literature surrounding these issues will be briefly summarized, and the translational implications of an intersectional hypothesis of PD pathogenesis discussed.
帕金森病（PD）是第二常见的神经退行性疾病，使全球数百万人致残。尽管 PD 构成了巨大的威胁，但目前尚无治愈方法或减缓疾病进展的手段。造成这种差距的原因是我们对导致发病机制的因素的理解不完整。过去几十年的研究表明，细胞自主和非细胞自主过程都有助于 PD 症状下的神经元功能障碍。本文的论点是，这些过程的交叉点控制着 PD 病理模式。对黑质致密部（SNc）多巴胺能神经元的研究表明，这些神经元具有长而高度分支的轴突、自主活动和升高的线粒体氧化应激等特征，这使它们易受发病机制的非细胞自主驱动因素的影响，如错误折叠的α-突触核蛋白（α-SYN）和炎症。将简要总结围绕这些问题的文献，并讨论 PD 发病机制的交叉假说的转化意义。
