Astrocyte dysfunction in Parkinson's Check for updates disease:from the perspectives of transmittedα-synuclein and genetic modulation

摘要

Parkinson's disease(PD)is a common neurodegenerative disorder that primarily affects the elderly.While the etiology of PD is likely multifactorial with the involvement of genetic,environmental,aging and other factors,α-synuclein(α-syn)pathology is a pivotal mechanism underlying the development of PD.In recent years,astrocytes have attracted considerable attention in the field.Although astrocytes perform a variety of physiological functions in the brain,they are pivotal mediators ofα-syn toxicity since they internalizeα-syn released from damaged neurons,and this triggers an inflammatory response,protein degradation dysfunction,mitochondrial dysfunction and endoplasmic reticulum stress.Astrocytes are indispensable coordinators in the background of several genetic mutations,including PARK7,GBA1,LRRK2,ATP13A2,PINK1,PRKN and PLA2G6.As the most abundant glial cells in the brain,functional astrocytes can be replenished and even converted to functional neurons.In this review,we discuss astrocyte dysfunction in PD with an emphasis onα-syn toxicity and genetic modulation and conclude that astrocyte replenishment is a valuable therapeutic approach in PD.