K.R.E.D: New insights into the regulation of the CNS water channel aquaporin-4: from cell biology to clinical trials

Kavli Research & Enterprise Discussions (K.R.E.D)

Our Kavli Research and Enterprise Discussion (K.R.E.D) will be given by Roslyn Bill. Roslyn Bill is a Professor of Biotechnology at Aston University, Birmingham, UK.

Roslyn's talk is entitled "New insights into the regulation of the CNS water channel aquaporin-4: from cell biology to clinical trials".

Date: 30 November 2023

Time: 15:00

Room: Phase 2 - Seminar Room 20-138

This is an event for University staff only.

Tea/coffee will be served prior to the event from 14:30 on the lower ground floor.

The abstract is below. 

Aquaporins facilitate the passive, bidirectional flow of water in all cells and tissues. In the brain and spinal cord, aquaporin-4 is highly expressed and enriched at astrocyte endfeet, synapses and the glia limitans. It facilitates the exchange of water across the blood-spinal cord and blood-brain barriers, controlling cell volume, extracellular space volume and astrocyte migration. The perivascular enrichment of aquaporin-4 is consistent with its central role in glymphatic function, although the mechanism by which that role is exerted remains unknown. Recently, we have demonstrated that aquaporin-4 localization is dynamically regulated at the subcellular level, affecting membrane water permeability. In animal models of ageing, stroke, traumatic injury and sleep disruption, impairment of glymphatic function is associated with changes in perivascular aquaporin-4 localization. Each of these conditions represent established and emerging risk factors in developing neurodegeneration. Brain and spinal cord oedema are caused by the influx of water through aquaporin-4 in response to osmotic imbalances that occur following insults such as traumatic injury, stroke or tumour development. We have demonstrated that reducing dynamic subcellular relocalization of aquaporin-4 to the blood-spinal cord or blood-brain barriers reduces oedema and accelerates functional recovery in rodent injury models. Given the difficulties in developing pore-blocking aquaporin-4 inhibitors or activators and controversies in the field over the status of many proposed molecules, targeting dynamic aquaporin-4 subcellular relocalization provides a novel new approach to modulating aquaporin-4 function. This approach also opens up new treatment avenues for CNS oedema, neurovascular and neurodegenerative diseases, and provides a framework to address fundamental unanswered questions about water homeostasis in health and disease.