Aqp4 stop codon readthrough facilitates amyloid-β clearance from the brain

Aug 24, 2022Brain : a journal of neurology

Aqp4 protein production beyond the usual stop helps clear amyloid-β from the brain

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Abstract

The Aquaporin 4 variant AQP4X mediates amyloid beta clearance in the brain.

  • Aquaporin 4 is involved in the clearance of amyloid beta, with its perivascular fraction decreased in Alzheimer's disease.
  • An elongated variant of Aquaporin 4, AQP4X, is generated through a stop codon readthrough event and is found exclusively in perivascular regions.
  • AQP4X has been shown to mediate the clearance of amyloid beta based on findings from knockout mice.
  • Small molecule compounds that enhance the readthrough of the Aquaporin 4 sequence have been identified through high-throughput screening.
  • In vivo experiments demonstrate that these compounds enhance brain amyloid beta clearance, relying on the presence of AQP4X.

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