Aquaporin 4 (AQP4) (AQP4)

Aquaporin 4 (AQP4) is a member of the aquaporin family of integral membrane proteins that facilitate the rapid transport of water across cell membranes in response to osmotic gradients [1.2.1]. While most prominently known as the primary water channel in the central nervous system (CNS), AQP4 is also expressed in the colonic epithelium, specifically in the basolateral membranes of surface epithelial cells and crypts [1.3.1]. In the colon, AQP4 plays a significant role in transepithelial water transport and the regulation of fecal water content, with its absence or downregulation linked to altered bowel habits [1.3.2]. In the context of oncology, AQP4 is frequently overexpressed in colon cancer tissues compared to normal mucosa, where it promotes tumor cell migration, invasion, and metastasis, serving as a potential prognostic biomarker [1.1.1, 1.3.3]. Furthermore, AQP4 is the primary autoantigen in Neuromyelitis Optica Spectrum Disorder (NMOSD), an inflammatory demyelinating disease where autoantibodies (AQP4-IgG) trigger complement-mediated astrocyte damage [1.4.5]. Therapeutic strategies include the use of monoclonal antibodies to prevent AQP4-IgG-mediated injury and experimental small molecules or siRNA to modulate its water transport and oncogenic functions [1.4.2, 1.1.4].

Other names

AQP-4Mercurial-insensitive water channelMIWCWCH4HMIWC2

Inhibition of the complement cascade (C5), depletion of CD19+ B-cells, or blockade of IL-6 signaling to prevent AQP4-autoantibody-mediated damage; experimental direct inhibition of the water channel pore or competitive blockade of autoantibody binding.