Abstract
Aquaporins facilitate the passive transport of water, solutes, or ions across biological membranes. They are implicated in diverse pathologies including brain edema following stroke or trauma, epilepsy, cancer cell migration and tumor angiogenesis, metabolic disorders, and inflammation. Despite this, there is no aquaporin-targeted drug in the clinic and aquaporins have been perceived to be intrinsically non-druggable targets. Here we challenge this idea, as viable routes to inhibition of aquaporin function have recently been identified, including targeting their regulation or their roles as channels for unexpected substrates. Identifying new drug development frameworks for conditions associated with disrupted water and solute homeostasis will meet the urgent, unmet clinical need of millions of patients for whom no pharmacological interventions are available.
Highlights
Diseases of aquaporin dysfunction Water is essential for life
The small diameter of all aquaporin pores, together with the chemical properties of Aquaporins are attractive targets for therapeutic intervention in the diverse conditions associated with water and solute dyshomeostasis that affect millions of patients worldwide every year
As most mammalian aquaporins are recycled between the plasma membrane and endosomal compartments, we propose that aquaporin plasma membrane abundance should be measured to ensure that any measured changes in aquaporin function are due to inhibition of channel function and not to changes in aquaporin membrane abundance
Summary
Aquaporins facilitate the passive transport of water, solutes, or ions across biological membranes They are implicated in diverse pathologies including brain edema following stroke or trauma, epilepsy, cancer cell migration and tumor angiogenesis, metabolic disorders, and inflammation. There is no aquaporin-targeted drug in the clinic and aquaporins have been perceived to be intrinsically nondruggable targets We challenge this idea, as viable routes to inhibition of aquaporin function have recently been identified, including targeting their regulation or their roles as channels for unexpected substrates. Identifying new drug development frameworks for conditions associated with disrupted water and solute homeostasis will meet the urgent, unmet clinical need of millions of patients for whom no pharmacological interventions are available. Identifying new aquaporin-targeted drugs for conditions associated with disrupted water and solute homeostasis will meet an urgent, unmet clinical need as no pharmacological interventions are currently available.
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