Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis - Archive ouverte HAL Access content directly
Journal Articles Brain - A Journal of Neurology Year : 2021

Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis

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Mootaz M Salman
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  • PersonId : 1112359
Philip Kitchen
  • Function : Author
  • PersonId : 1112360
Andrea Halsey
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Marie Xun Wang
  • Function : Author
Susanna Tornroth-Horsefield
  • Function : Author
Alex C Conner
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Jeffrey J Iliff
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Roslyn M Bill
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Abstract

Aquaporin channels facilitate bidirectional water flow in all cells and tissues. AQP4 is highly expressed in astrocytes. In the CNS, it is enriched in astrocyte endfeet, at synapses, and at the glia limitans, where it mediates water exchange across the blood-spinal cord and blood-brain barriers (BSCB/BBB), and controls cell volume, extracellular space volume, and astrocyte migration. Perivascular enrichment of AQP4 at the BSCB/BBB suggests a role in glymphatic function. Recently, we have demonstrated that AQP4 localization is also dynamically regulated at the subcellular level, affecting membrane water permeability. Ageing, cerebrovascular disease, traumatic CNS injury, and sleep disruption are established and emerging risk factors in developing neurodegeneration, and in animal models of each, impairment of glymphatic function is associated with changes in perivascular AQP4 localization. CNS oedema is caused by passive water influx through AQP4 in response to osmotic imbalances. We have demonstrated that reducing dynamic relocalization of AQP4 to the BSCB/BBB reduces CNS oedema, and accelerates functional recovery in rodent models. Given the difficulties in developing pore-blocking AQP4 inhibitors, targeting AQP4 subcellular localization opens up new treatment avenues for CNS oedema, neurovascular and neurodegenerative diseases, and provides a framework to address fundamental questions about water homeostasis in health and disease.
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hal-03366666 , version 1 (05-10-2021)

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Attribution - CC BY 4.0

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Mootaz M Salman, Philip Kitchen, Andrea Halsey, Marie Xun Wang, Susanna Tornroth-Horsefield, et al.. Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis. Brain - A Journal of Neurology , 2021, ⟨10.1093/brain/awab311/6367770⟩. ⟨hal-03366666⟩

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