Ablating N-acetylaspartate prevents leukodystrophy in a Canavan disease model

Ann Neurol. 2015 May;77(5):884-8. doi: 10.1002/ana.24392. Epub 2015 Mar 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / deficiency
  • Aspartic Acid / genetics
  • Aspartic Acid / metabolism
  • Canavan Disease / genetics
  • Canavan Disease / metabolism*
  • Canavan Disease / prevention & control*
  • Disease Models, Animal*
  • Female
  • Male
  • Mice
  • Mice, Knockout

Substances

  • Aspartic Acid
  • N-acetylaspartate