Glymphatic system dysfunction: a link between sleep disorders and neurodegeneration.

RATIONALE: Sleep disturbances are closely associated with cognitive decline and an increased risk of neurodegenerative diseases in humans. This association may be mediated by glymphatic dysfunction, which could ultimately lead to cognitive deterioration. OBJECTIVES: This review aims to provide an overview of current research on the impact of sleep on the functions of the glymphatic system. It analyzes the regulatory roles of the sleep-wake cycle and neurovascular coupling (NVC), along with molecular mechanisms such as astrocytic calcium signaling and aquaporin-4 (AQP4) polarization, intending to identify potential targets for preventing and alleviating cognitive decline and neurodegenerative diseases. RESULTS: This review summarizes the intrinsic mechanisms by which sleep regulates the metabolic waste clearance capacity of the glymphatic system, highlighting its central role in regulating glymphatic function. Furthermore, it provides a detailed overview of the significant contributions of NVC and astrocytes within this regulatory framework, as well as novel interventions targeting neurodegenerative diseases. CONCLUSIONS: Given that sleep disturbances are a significant factor affecting human cognitive function and neurodegenerative diseases, it is imperative to advance research in this field. Efforts should focus on deepening our understanding of the glymphatic system and its regulatory mechanisms while integrating clinical practice to explore new research directions.