Aqp4, an aquaporin protein, is a water channel that plays a crucial role in water and electrolyte regulation, a vital homeostatic function. It is mainly expressed in the central nervous system, especially in the foot processes of astrocytes around capillaries, beneath the pia matter, and lining the ventricles. Aqp4 is involved in the "glymphatic system" concept proposed in 2012, where it may facilitate the continuous interchange between cerebrospinal fluid and brain interstitial fluid, guiding proteins and metabolites away from the CNS, thus contributing to brain homeostasis [1,2].

In preclinical AQP4 knockout (KO) studies, AQP4 expression was found necessary to prevent the effect of stress and inflammation on reduced neurogenesis and gliogenesis, and increased apoptosis and depressive-like behaviors. Also, in multiple sclerosis-related Neuromyelitis optica spectrum disorder (NMOSD), most patients have pathogenic antibodies targeting AQP4, highlighting its role in this disease's pathophysiology [4,3].

In conclusion, Aqp4 is essential for brain water homeostasis and waste clearance in the CNS. Aqp4 KO mouse models have revealed its role in preventing stress-and inflammation-induced adverse neural effects and in the pathogenesis of NMOSD. Understanding Aqp4 can potentially lead to new drug development for sleep, mental disorders, and neurodegenerative diseases [1,2,4].

References:

1. Yasui, Masato. . [Aquaporin4 (AQP4) in brain disorder]. In Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 153, 231-234. doi:10.1254/fpj.153.231. https://pubmed.ncbi.nlm.nih.gov/31092756/

2. Mohaupt, Pablo, Vialaret, Jérôme, Hirtz, Christophe, Lehmann, Sylvain. 2023. Readthrough isoform of aquaporin-4 (AQP4) as a therapeutic target for Alzheimer's disease and other proteinopathies. In Alzheimer's research & therapy, 15, 170. doi:10.1186/s13195-023-01318-2. https://pubmed.ncbi.nlm.nih.gov/37821965/

3. Wright, Sukhvir K, Wassmer, Evangeline, Vincent, Angela. 2021. Pathogenic antibodies to AQP4: Neuromyelitis optica spectrum disorder (NMOSD). In Biochimica et biophysica acta. Biomembranes, 1863, 183772. doi:10.1016/j.bbamem.2021.183772. https://pubmed.ncbi.nlm.nih.gov/34509490/

4. Genel, Oktay, Pariante, Carmine M, Borsini, Alessandra. 2021. The role of AQP4 in the pathogenesis of depression, and possible related mechanisms. In Brain, behavior, and immunity, 98, 366-377. doi:10.1016/j.bbi.2021.08.232. https://pubmed.ncbi.nlm.nih.gov/34474133/