Sleep-circadian modulation of autophagy and glymphatic function: failure of coordinated brain clearance in Parkinson’s disease

Parkinson’s disease (PD) involves α-synuclein accumulation and progressive neurodegeneration. This review proposes that PD reflects failure of sleep-circadian regulated brain clearance network integrating intracellular autophagy and extracellular glymphatic transport across neurons, glia, and blood-brain-barrier. Disruption of sleep-architecture and circadian-timing desynchronizes these processes, impairing protein clearance and promoting pathology. This framework positions sleep-circadian dysfunction as an upstream mechanism, suggesting that restoring sleep-circadian regulation may improve protein clearance and support disease-modifying strategies.