Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, United States.
Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, United States.
Prog Brain Res. 2020;252:169-216. doi: 10.1016/bs.pbr.2019.10.006. Epub 2019 Dec 5.
Parkinson's disease (PD) has classically been defined as a movement disorder, in which motor symptoms are explained by the aggregation of alpha-synuclein (α-syn) and subsequent death of dopaminergic neurons of the substantia nigra pars compacta (SNpc). More recently, the multisystem effects of the disease have been investigated, with the immune system being implicated in a number of these processes in the brain, the blood, and the gut. In this review, we highlight the dysfunctional immune system found in both human PD and animal models of the disease, and discuss how genetic risk factors and risk modifiers are associated with pro-inflammatory immune responses. Finally, we emphasize evidence that the immune response drives the pathogenesis and progression of PD, and discuss key questions that remain to be investigated in order to identify immunomodulatory therapies in PD.
帕金森病(PD)经典地被定义为一种运动障碍,其中运动症状可归因于α-突触核蛋白(α-syn)的聚集,以及随后的黑质致密部多巴胺能神经元的死亡。最近,人们研究了该疾病的多系统影响,发现免疫系统参与了大脑、血液和肠道中的许多这些过程。在这篇综述中,我们强调了在人类 PD 和疾病动物模型中发现的功能失调的免疫系统,并讨论了遗传风险因素和风险修饰因子如何与促炎免疫反应相关。最后,我们强调了免疫反应驱动 PD 的发病机制和进展的证据,并讨论了为了确定 PD 的免疫调节疗法仍需研究的关键问题。