Department of Neuroscience, Vickie and Jack Farber Institute of Neuroscience, Thomas Jefferson University, Philadelphia, PA, USA.
Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
J Parkinsons Dis. 2021;11(1):31-43. doi: 10.3233/JPD-202279.
Parkinson's disease (PD) is thought to be caused by a combination of genetic and environmental factors. Bacterial or viral infection has been proposed as a potential risk factor, and there is supporting although not entirely consistent epidemiologic and basic science evidence to support its role. Encephalitis caused by influenza has included parkinsonian features. Epidemiological evidence is most compelling for an association between PD and hepatitis C virus. Infection with Helicobacter pylori may be associated not only with PD risk but also response to levodopa. Rapidly evolving knowledge regarding the role of the microbiome also suggests a role of resident bacteria in PD risk. Biological plausibility for the role for infectious agents is supported by the known neurotropic effects of specific viruses, particular vulnerability of the substantia nigra and even the promotion of aggregation of alpha-synuclein. A common feature of implicated viruses appears to be production of high levels of cytokines and chemokines that can cross the blood-brain barrier leading to microglial activation and inflammation and ultimately neuronal cell death. Based on multiple avenues of evidence it appears likely that specific bacterial and particularly viral infections may increase vulnerability to PD. The implications of this for PD prevention requires attention and may be most relevant once preventive treatments for at-risk populations are developed.
帕金森病(PD)被认为是由遗传和环境因素共同引起的。细菌或病毒感染已被提出为一个潜在的危险因素,虽然有支持的但并非完全一致的流行病学和基础科学证据支持其作用。由流感引起的脑炎包括帕金森病的特征。与丙型肝炎病毒(HCV)之间的关联,具有最强有力的流行病学证据。幽门螺杆菌(H. pylori)的感染不仅与 PD 风险有关,而且与左旋多巴的反应有关。关于微生物组作用的快速发展知识也表明常驻细菌在 PD 风险中的作用。感染因子的生物学可能性得到了特定病毒的已知神经毒性作用、黑质的特殊脆弱性,甚至α-突触核蛋白聚集的促进的支持。所涉及的病毒的一个共同特征似乎是产生高水平的细胞因子和趋化因子,这些细胞因子和趋化因子可以穿过血脑屏障,导致小胶质细胞激活和炎症,最终导致神经元细胞死亡。基于多种证据,似乎特定的细菌,特别是病毒感染可能会增加患 PD 的脆弱性。这对 PD 预防的影响需要引起重视,一旦为高危人群开发出预防治疗方法,这种影响可能最为相关。