July 27th, 2026
As the name might suggest, aquaporin proteins facilitate the transfer of water molecules across cell membranes. This is important in a broad range of contexts, such as the operation of the blood-brain barrier that wraps blood vessels that pass through the brain, and in the drainage of cerebrospinal fluid from the brain into the body. One of the paths by which cerebrospinal fluid exits the brain, carrying away metabolic waste with it, is the glymphatic system. Glymphatic vessels run parallel to the blood vessels that enter and exit the brain. Research is making it increasingly apparent that drainage of cerebrospinal fluid is vital to the health of the brain. Unfortunately this drainage becomes progressively ever more impaired with advancing age, and this is thought to contribute to the buildup of protein aggregates and other forms of metabolic waste in the brain, contributing to inflammation, cell dysfunction, and neurodegenerative conditions.
In today's open access paper, researchers build on past work on the manipulation of aquaporin 4 (AQP4) activity in the glymphatic system. A small molecule compound TGN-073 increases the activity of AQP4 via a mechanism that isn't understood, but may involve altering the structure of AQP4 to broaden the size of the pores it creates in the cell membrane. Other work has shown that different isoforms and thus structures of AQP4 are more effective than the usual version, for example. Here, researchers show that this increased AQP4 activity does in fact help to reduce neurodegenerative pathology in mice, supporting the importance of failing cerebrospinal fluid drainage in the development and progression of neurodegenerative conditions.
