Cross-talk between neuroinflammation and α-synuclein aggregation: The central role of the cGAS-STING pathway in Parkinson's disease.

Parkinson's Disease (PD) is a common neurodegenerative disorder with a complex and incompletely elucidated pathogenesis. Dysregulated immunity plays a pivotal role in the initiation and progression of the disease. The cyclic guanosine monophosphate (GMP)- adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway, an intracellular innate immune signaling cascade that has attracted considerable attention in recent years, exerts crucial functions in sensing pathogen invasion and endogenous damage-associated molecular patterns (DAMPs), as well as regulating immune responses. This review thoroughly explores the role of the cGAS-STING pathway in PD immune regulation. It first details the pathway's structural components and activation mechanism, then analyzes its aberrant activation under PD pathological conditions. Furthermore, it discusses in detail the specific mechanisms underlying its role in PD immune regulation, including its impacts on microglial activation, inflammatory cytokine release, α-synuclein (α-syn) aggregation and clearance, as well as neuronal survival. Meanwhile, it summarizes the current research progress in targeting the cGAS-STING pathway for PD treatment. Finally, it points out the existing challenges and future research directions in this field, aiming to provide novel insights and theoretical foundations for investigating PD pathogenesis and developing clinical therapeutic strategies.