Α-Synuclein in Parkinson's Disease: Does a Prion-Like Mechanism of Propagation from Periphery to the Brain Play a Role?. (August 2021)

• Record Type: Journal Article
• Authors: Zheng, Huimin; Shi, Changhe; Luo, Haiyang; Fan, Liyuan; Yang, Zhihua; Hu, Xinchao; Zhang, Zhongxian; Zhang, Shuo; Hu, Zhengwei; Fan, Yu; Yang, Jing; Mao, Chengyuan; Xu, Yuming
• Is Part Of: Neuroscientist. Volume 27:Number 4(2021)
• Page Start: 367
• Page End: 387
• Publication Date: 2021-08
• Subjects: Parkinson's disease -- prion-like propagation -- α-synuclein -- pathway -- prionoid; Neurosciences -- Periodicals; Neurology -- Periodicals; Neurobiology -- Periodicals; 616.8005
• DOI: 10.1177/1073858420943180
• Languages: English
• ISSNs: 1073-8584

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative diseases, defined as motor and non-motor symptoms associated with the loss of dopaminergic neurons and a decreased release of dopamine (DA). Currently, PD patients are believed to have a neuropathological basis denoted by the presence of Lewy bodies (LBs) or Lewy neurites (LNs), which mostly comprise α-synuclein (α-syn) inclusions. Remarkably, there is a growing body of evidence indicating that the inclusions undergo template-directed aggregation and propagation via template-directed among the brain and peripheral organs, mainly in a prion-like manner. Interestingly, some studies reported that an integral loop was reminiscent of the mechanism of Parkinson's disease, denoting that α-syn as prionoid was transmitted from the periphery to the brain via specific pathways. Also the systematic life cycle of α-syn in the cellular level is illustrated. In this review, we critically assess landmark evidence in the field of Parkinson's disease with a focus on the genesis and prion-like propagation of the α-syn pathology. The anatomical and cell-to-cell evidences are discussed to depict the theory behind the propagation and transferred pathways. Furthermore, we highlight effective therapeutic perspectives and clinical trials targeting prion-like mechanisms. Major controversies surrounding this topic are also discussed.