Uncoupling N-acetylaspartate from brain pathology: implications for Canavan disease gene therapy.

ABSTRACT: N-Acetylaspartate (NAA) is the second most abundant organic metabolite in the brain, but its physiological significance remains enigmatic. Toxic NAA accumulation appears to be the key factor for neurological decline in Canavan disease-a fatal neurometabolic disorder caused by deficiency in the NAA-degrading enzyme aspartoacylase. To date clinical outcome of gene replacement therapy for this spongiform leukodystrophy has not met expectations. To identify the target tissue and cells for maximum anticipated treatment benefit, we employed comprehensive phenotyping of novel mouse models to assess cell type-specific consequences of NAA depletion or elevation. We show that NAA-deficiency causes neurological deficits affecting unconscious defensive reactions aimed at protecting the body from exter

SUBMITTER: von Jonquieres G 

PROVIDER: S-EPMC5756261 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature