Aquaporin4 (AQP4) in brain disorder

Two third of our body is composed of water molecules. Regulation of water and electrolytes is indeed the most important homeostatic functions. Many diseases, such as heart failure, are associated with disturbance in fluid homeostasis. Surprisingly, water dynamics inside the brain is still largely unknown. In 2012, a new concept referred as “glymphatic system” was proposed by Nedergaard’s group, where aquaporin4 (AQP4) may play an important role as well as sleep. AQP4 is mainly expressed in the central nervous system, especially in the foot processes of astrocytes; surrounding the capillary, beneath pia matter and lining the ventricles. The unique distribution of AQP4 suggest that AQP4 might play a role in brain water homeostasis. The concept of “glymphatic system” is still controversial, and needs to be clarified with new experimental data. This approach will lead to the better understanding of roles of astrocytes in neurodegenerative diseases and pharmacokinetics inside the brain, and eventually will facilitate the development of new drugs for sleep or mental disorders. It has been accumulating evidence that sleep disturbance is related to several kinds of chronic diseases such as hypertension and diabetes. In addition, the number of patients with dementia are significantly increasing. It is therefore critical to understand the physiological and pathological mechanisms of brain lymphatic system from the medical and social point of views. Here I will discuss about the roles of AQP4 in neurodegenerative diseases and introduce new knowledge regarding to “glymphatic system”.