Astrocytic dysfunction in Parkinson's disease pathogenesis: focusing on alpha-synuclein.

Parkinson’s disease (PD), a prevalent age-related neurodegenerative movement disorder, is fundamentally driven by the accumulation of abnormal alpha-synuclein (α-Syn) within dopaminergic neurons of the substantia nigra pars compacta (SNpc). While astrocytes normally protect neurons through antioxidant release, anti-inflammatory actions influenced by microglia, and dopaminergic receptor signaling, a critical shift occurs as α-Syn progressively accumulates within astrocytes themselves. This intracellular α-Syn buildup is central to transforming astrocytes from a protective state into a detrimental one. Genetic mutations linked to PD further impair astrocytic functions like antioxidant defense. The precise mechanisms by which α-Syn accumulation drives this harmful phenotypic shift in astrocytes remain unclear, but it significantly worsens PD pathology. This review examines the dual roles of astrocytes in PD pathogenesis, emphasizing α-Syn’s pivotal role in their functional transformation.