Astrocytes orchestrate neuroprotection and pathogenesis via bidirectional neuronal interactions in Parkinson's...

Parkinson's disease (PD), a prevalent neurodegenerative disorder, is characterized by the degeneration of dopaminergic neurons in the substantia nigra and striatum of the midbrain, manifesting as distinct motor impairments. While conventional theories attribute PD's development to neuronal damage, astrocytes have garnered significant attention for their potential protective role. As the most abundant glial cells in the central nervous system (CNS), astrocytes may exert neuroprotective effects through mechanisms including secretion of neurotrophic factors, regulation of the blood-brain barrier (BBB), and maintenance of water-electrolyte balance. Recent studies indicate that mutations in PD-associated genes may induce functional alterations in astrocytes. Activated astrocytes accelerate neuronal degeneration by releasing inflammatory mediators, disrupting glutamate homeostasis, and triggering oxidative stress. Furthermore, bidirectional regulatory interactions exist between astrocytes and both dopaminergic neurons and other glial cells in PD. This review systematically summarizes current research on astrocyte involvement in PD pathology and their neuronal interaction mechanisms, further exploring their interconnections to elucidate disease pathogenesis. The findings provide novel theoretical frameworks for developing astrocyte-targeted therapies and preventive strategies against PD.