Astrocytes in Parkinson's Disease: From Guardians to Accomplices

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of nigral dopaminergic neurons and misfolded α‑synuclein (α‑Syn) aggregation. However, increasing evidence indicates that astrocytes occupy a central position in the multifactorial pathogenesis of PD. As the most abundant glial cells in the Central Nervous System (CNS), astrocytes maintain neural homeostasis via neurotransmitter clearance, ion balance, metabolic support, synaptic regulation, and blood-brain barrier (BBB) integrity. In early PD, astrocytes exert neuroprotective effects; with disease progression, persistent pathological stimuli-including aggregated α-Syn, chronic neuroinflammation, mitochondrial dysfunction, oxidative stress, and iron dyshomeostasis-drive astrocytes into a reactive, neurotoxic state. This review systematically summarizes how astrocytes regulate α-Syn handling, mitochondrial function, neuroinflammation, and oxidative stress in PD, explaining how these pathways reshape astrocyte states across disease stages, and highlights stage-dependent dual roles of astrocytes as guardians and accomplices, with implications for astrocyte-targeted therapies.