Astrocyte dysfunction in Parkinson's disease: from the perspectives of transmitted α-synuclein and genetic modulation

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, alpha-synuclein (alpha-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 of alpha-syn toxicity since they internalize alpha-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 on alpha-syn toxicity and genetic modulation and conclude that astrocyte replenishment is a valuable therapeutic approach in PD.

Automated summary

Parkinson's disease is a common neurodegenerative disorder that primarily affects the elderly, with alpha-synuclein pathology being a pivotal mechanism underlying its development. Astrocytes play a crucial role in PD by internalizing alpha-synuclein from damaged neurons, triggering various adverse effects. The replenishment of functional astrocytes is seen as a valuable therapeutic approach in treating PD.