The role and mechanism of abnormal accumulation and transmission of alpha-synuclein in the pathogenesis and progression of Parkinson′s disease / 中华神经科杂志

ABSTRACT

Parkinson′s disease (PD) is the most common age-related neurodegenerative disease, which has the effects on the patients′ quality of life and brings a huge burden to the society and family. The pathological feature of PD is the abnormal accumulation of alpha-synuclein (α-syn) in the brain of substantia nigra-striatum, mediating the death of dopaminergic neurons. However, further studies have found that α-syn mediates the abnormal function of astrocytes leading to the destruction of the blood-brain barrier and the release of inflammatory factors caused by microglia, which are related to the pathogenesis of PD. Therefore, neurons, glial cells, and blood vessels as a whole named neurovascular unit can better reflect the pathophysiological environment of PD and reveal the PD pathogenesis. Studies have detected the ways of α-syn transmission, such as prion-like, tunneling nanotubes, exosomes, are connected with the pathogenesis and progression of PD. The Braak stage and the prospective cohort of early PD provide a view that the peripheral α-syn to the central nervous system may be an another important way to mediate the pathogenesis and progression of PD. The research about the abnormal aggregation and spread of α-syn can provide the new theory for the pathogenesis of PD and the new disease modifying therapy of PD. This article reviews the role of abnormal aggregation and transmission of α-syn in the pathogenesis of PD.