AQP4

Aquaporin 4 (AQP4) at astrocyte perivascular endfeet is essential for brain water balance, and its dysfunction contributes to neurological pathologies, including impaired amyloid clearance in Alzheimer’s disease and peritumoral edema in glioblastoma. Novel AQP4 isoforms (AQP4ex) exhibit distinct water permeability, osmotic sensitivity, and subcellular localization, but their specific roles remain unknown. Using isoform-specific transgenic mice, advanced microscopy, cell assays and proteomics, we will investigate how individual and combined isoforms regulate astrocyte water transport, protein interactions, and glymphatic flow. These studies will reveal fundamental mechanisms of brain water and solute homeostasis and identify potential targets for therapeutic modulation of edema and impaired clearance.