Ablating N-acetylaspartate prevents leukodystrophy in a Canavan disease model.

Guo, Fuzheng; Bannerman, Peter; Mills Ko, Emily; Miers, Laird; Xu, Jie; Burns, Travis; Li, Shuo; Freeman, Ernest et al. · Ann Neurol · 2015

basic_science · Level V

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Abstract

Canavan disease is caused by inactivating ASPA (aspartoacylase) mutations that prevent cleavage of N-acetyl-L-aspartate (NAA), resulting in marked elevations in central nervous system (CNS) NAA and progressively worsening leukodystrophy. We now report that ablating NAA synthesis by constitutive genetic disruption of Nat8l (N-acetyltransferase-8 like) permits normal CNS myelination and prevents leukodystrophy in a murine Canavan disease model.

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