Alpha-Synuclein and Microglia in Parkinson's Disease: From Pathogenesis to Therapeutic Prospects

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor symptoms and non-motor features. A hallmark of PD is the misfolding and accumulation of alpha-synuclein (α-syn), which triggers neuroinflammation and drives neurodegeneration. Microglia, brain cells that play a central role in neuroinflammatory responses and help clear various unnecessary molecules within the brain, thus maintaining the brain's internal environment, respond to α-syn through mechanisms involving inflammation, propagation, and clearance. This review delves into the complex interplay between α-syn and microglia, elucidating how these interactions drive PD pathogenesis. Furthermore, we discuss emerging therapeutic strategies targeting the α-syn-microglia axis, with a focus on modulating microglial functions to mitigate neuroinflammation, enhance clearance, and prevent α-syn propagation, emphasizing their potential to slow PD progression.