Intraneuronal N‐acetylaspartate supplies acetyl groups for myelin lipid synthesis: evidence for myelin‐associated aspartoacylase

@article{Chakraborty2001IntraneuronalNS,
  title={Intraneuronal N‐acetylaspartate supplies acetyl groups for myelin lipid synthesis: evidence for myelin‐associated aspartoacylase},
  author={G. Chakraborty and Praveen Mekala and Daniel Yahya and Gusheng Wu and R. Ledeen},
  journal={Journal of Neurochemistry},
  year={2001},
  volume={78}
}
Despite its growing use as a radiological indicator of neuronal viability, the biological function of N‐acetylaspartate (NAA) has remained elusive. This is due in part to its unusual metabolic compartmentalization wherein the synthetic enzyme occurs in neuronal mitochondria whereas the principal metabolizing enzyme, N‐acetyl‐l‐aspartate amidohydrolase (aspartoacylase), is located primarily in white matter elements. This study demonstrates that within white matter, aspartoacylase is an integral… Expand
Bimodal occurrence of aspartoacylase in myelin and cytosol of brain
TLDR
Evidence is presented that the membrane‐bound form of ASPA is intrinsic to purified myelin membranes and utilization of acetyl groups liberated by myelin‐localized ASPA for lipid synthesis within the myelin sheath might be selective and could explain the deficit of myelin lipids in animals lacking ASPA. Expand
Fatty acid synthesizing enzymes intrinsic to myelin.
A recent study showing incorporation of acetyl groups from neuronal N-acetylaspartate into myelin lipids suggested the presence of fatty acid synthesizing enzymes in myelin that utilize the acetylExpand
N-acetylaspartate supports the energetic demands of developmental myelination via oligodendroglial aspartoacylase
TLDR
Effects on brain energy observed following AAV-Olig001-aspartoacylase gene therapy are shown to be consistent with a metabolic profile observed in mild cases of Canavan disease, implicating NAA in the maintenance of energetic integrity during myelination via oligodendroglial aspartoACYlase. Expand
N-Acetylaspartate synthase is bimodally expressed in microsomes and mitochondria of brain.
TLDR
The tentative conclusion is that ANAT is bimodally targeted to MIT and a component of MIC-likely endoplasmic reticulum. Expand
Aspartoacylase Supports Oxidative Energy Metabolism during Myelination
  • J. Francis, L. Strande, V. Markov, P. Leone
  • Biology, Medicine
  • Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2012
TLDR
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 suggests a role for NAA in the maintenance of metabolic integrity in oligodendedrocytes that may be of relevance to the strong association between NAA and neuronal viability. Expand
N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology
TLDR
Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptides N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain, and it is proposed that N AA may also be involved in brain nitrogen balance. Expand
Myelin Lipid Abnormalities in the Aspartoacylase-Deficient Tremor Rat
TLDR
The dysmyelination that results from inactivation of ASPA is thus characterized by selective decreases as well as some increases in specific lipids. Expand
The neuronal metabolite NAA regulates histone H3 methylation in oligodendrocytes and myelin lipid composition
TLDR
Data suggest that neuronal-derived NAA signals through epigenetic mechanisms in oligodendrocytes to support or maintain myelination. Expand
Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease.
TLDR
It is demonstrated that myelin lipid synthesis is significantly compromised in CD and direct evidence that defective myelin synthesis, resulting from a deficiency of NAA-derived acetate, is involved in the pathogenesis of CD is provided. Expand
Oligodendrocytes Do Not Export NAA-Derived Aspartate In Vitro
TLDR
It is reported here that aspartoacylase mRNA expression increases when primary rat oligodendrocyte progenitor cells (OPCs) differentiate into mature cells in culture and resolved the controversy concerning the possible release of aspartate to the medium. Expand
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The experiments suggest that NAA transport in brain parenchyma occurs by a novel type of sodium‐dependent carrier that is present only in glial cells. Expand
ACETATE METABOLISM IN THE NERVOUS SYSTEM. N‐ACETYL‐l‐ASPARTIC ACID AND THE BIOSYNTHESIS OF BRAIN LIPIDS *
TLDR
Data are presented which show that N-acetyl-L-aspartic acid provides acetyl groups for lipid biosynthesis in myelinating rat brain in vivo and an attempt was made to determine whether the active acetate from the two sources enters similar pools. Expand
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TLDR
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TLDR
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TLDR
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