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J Cereb Blood Flow Metab. 2012 Sep;32(9):1725-36. doi: 10.1038/jcbfm.2012.66. Epub 2012 May 23.

Aspartoacylase supports oxidative energy metabolism during myelination.

Author information

1
Cell and Gene Therapy Center, Department of Cell Biology, University of Medicine and Dentistry of NJ, Stratford, New Jersey 08084, USA. francijs@umdnj.edu

Abstract

The inherited leukodystrophy Canavan disease arises due to a loss of the ability to catabolize N-acetylaspartic acid (NAA) in the brain and constitutes a major point of focus for efforts to define NAA function. Accumulation of noncatabolized NAA is diagnostic for Canavan disease, but contrasts with the abnormally low NAA associated with compromised neuronal integrity in a broad spectrum of other clinical conditions. Experimental evidence for NAA function supports a role in white matter lipid synthesis, but does not explain how both elevated and lowered NAA can be associated with pathology in the brain. We have undertaken a systematic analysis of postnatal development in a mouse model of Canavan disease that delineates development and pathology by identifying markers of oxidative stress preceding oligodendrocyte loss and dysmyelination. These data suggest a role for NAA in the maintenance of metabolic integrity in oligodendrocytes that may be of relevance to the strong association between NAA and neuronal viability. N-acetylaspartic acid is proposed here to support lipid synthesis and energy metabolism via the provision of substrate for both cellular processes during early postnatal development.

PMID:
22617649
PMCID:
PMC3434629
DOI:
10.1038/jcbfm.2012.66
[Indexed for MEDLINE]
Free PMC Article
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