Aquaporin-4 in glymphatic system, and its implication for central nervous system disorders

The clearance function is essential for maintaining brain tissue homeostasis, and the glymphatic system is the main pathway for removing brain interstitial solutes. Aquaporin-4 (AQP4) is the most abundantly expressed aquaporin in the central nervous system (CNS) and is an integral component of the glymphatic system. In recent years, many studies have shown that AQP4 affects the morbidity and recovery process of CNS disorders through the glymphatic system, and AQP4 shows notable variability in CNS disorders and is part of the pathogenesis of these diseases. Therefore, there has been considerable interest in AQP4 as a potential and promising target for regulating and improving neurological impairment. This review aims to summarize the pathophysiological role that AQP4 plays in several CNS disorders by affecting the clearance function of the glymphatic system. The findings can contribute to a better understanding of the self-regulatory functions in CNS disorders that AQP4 were involved in and provide new therapeutic alternatives for incurable debilitating neurodegenerative disorders of CNS in the future. •Aquaporin 4 as a target for regulating and improving neurological impairment.•Aquaporin 4 involved in brain edema, blood-brain barrier destruction and neuronal apoptosis.•Aquaporin 4 plays an important role in waste clearance through the glymphatic system.•Glymphatic system and Aquaporin 4 intervention may be a promising approach to prevent neurodegenerative diseases.