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Astroglial conditional Slc13a3 knockout is therapeutic in murine Canavan leukodystrophy.
Annals of Clinical and Translational Neurology 2024 January 29
Canavan disease is a leukodystrophy caused by ASPA mutations that diminish oligodendroglial aspartoacylase activity, and is characterized by markedly elevated brain concentrations of the aspartoacylase substrate N-acetyl-l-aspartate (NAA) and by astroglial and intramyelinic vacuolation. Astroglia express NaDC3 (encoded by SLC13A3), a sodium-coupled transporter for NAA and other dicarboxylates. Astroglial conditional Slc13a3 deletion in aspartoacylase-deficient Canavan disease model mice ("CD mice") reversed brain NAA elevation and improved motor function. These results demonstrate that astroglial NaDC3 contributes to brain NAA elevation in CD mice, and suggest that suppressing astroglial NaDC3 activity would ameliorate human Canavan disease.
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