Disease relevance of N-Acetyl-L-aspartic acid

• Reduced levels of N-acetylaspartate in malignant brain tumors [1].
• Canavan disease, an autosomal recessive leukodystrophy, is caused by deficiency of aspartoacylase and accumulation of N-acetylaspartic acid in brain [2].
• This result demonstrates for the first time, to our knowledge, a direct, quantitative link between a decrease in N-acetylaspartate and neuronal loss in a human neurodegenerative disease [3].
• The neuronal marker N-acetylaspartate was diffusely lower in the multiple sclerosis patients than in normal control subjects [4].
• Measurement of regional N-acetylaspartate after transient global ischemia in gerbils with and without ischemic tolerance: an index of neuronal survival [5].

Psychiatry related information on N-Acetyl-L-aspartic acid

• CONCLUSIONS: Electroconvulsive therapy is not likely to induce hippocampal atrophy or cell death, which would be reflected by a decrease in the N-acetylaspartate signal [6].
• The marked difference in the distribution of N-acetylaspartate to creatine between PPA and Alzheimer's disease suggests that proton magnetic resonance spectroscopy may help to differentiate between these two conditions [7].
• N-Acetylaspartate concentration in the anterior cingulate of maltreated children and adolescents with PTSD [8].
• Working memory deficits and levels of N-acetylaspartate in patients with schizophreniform disorder [9].
• In addition, they assessed the relationship between N-acetylaspartate levels and working memory deficits [9].

High impact information on N-Acetyl-L-aspartic acid

• Membrane-bound glutamate carboxypeptidase II (GCPII) is a zinc metalloenzyme that catalyzes the hydrolysis of the neurotransmitter N-acetyl-L-aspartyl-L-glutamate (NAAG) to N-acetyl-L-aspartate and L-glutamate (which is itself a neurotransmitter) [10].
• MAIN OUTCOME MEASURES: Estimates of gray and white matter concentrations for choline-containing compounds (Cho), creatine plus phosphocreatine, N-acetylaspartate (NAA), and myo-inositol (mI) [11].
• DESIGN: Left prefrontal cortex and left mediotemporal lobe voxels were assessed using proton magnetic resonance spectroscopy to provide the ratio of N-acetylaspartate (NAA) and choline-containing compounds to creatine and phosphocreatine (Cr) (NAA/Cr ratio) [12].
• BACKGROUND: We monitored the effect of electroconvulsive therapy (ECT) on the nuclear magnetic resonance-detectable metabolites N-acetylaspartate, creatine and phosphocreatine, and choline-containing compounds in the hippocampus by means of hydrogen 1 magnetic resonance spectroscopic imaging [6].
• Aspartoacylase catalyzes hydrolysis of N-acetyl-l-aspartate to aspartate and acetate in the vertebrate brain [13].

Chemical compound and disease context of N-Acetyl-L-aspartic acid

• We propose that abnormal signals from choline can indicate recent regional demyelination, while persistent abnormal signals from N-acetylaspartate can provide an index of irreversible damage in the nervous system [14].
• OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) showed decreased neuronal marker N-acetylaspartate and increased glial marker myo-inositol in subjects with chronic methamphetamine use and in subjects infected with HIV [15].
• A proton MRSI study of brain N-acetylaspartate level after 12 weeks of citalopram treatment in drug-naive patients with obsessive-compulsive disorder [16].
• To determine the stability of the signal from N-acetyl-L-aspartate, we used a model of graded hypoxia in rats to monitor the percentage changes from baseline of the peak heights for lactate, lipids, and N-acetyl-L-aspartate [17].
• Subcortical NAA correlated with performance on a variety of neuropsychological tests but not with Centers for Disease Control clinical stage, whereas high-thalamic Cho was associated with low CD4 lymphocyte counts [18].

Biological context of N-Acetyl-L-aspartic acid

• Prefrontal N-acetylaspartate, an in vivo MRI measure related to synaptic activity and closely correlated with tissue glutamate, was lower in SNP4 AA homozygotes [19].
• Sex differences in N-acetylaspartate correlates of general intelligence: an 1H-MRS study of normal human brain [20].
• In 38 healthy subjects, absolute concentrations of N-acetylaspartate (NAA) were measured as a main surrogate parameter for hippocampal neurochemistry on a 3-T scanner [21].
• There was a significant linear correlation between the time elapsed after infection and small, progressive decreases in the cell density/cell viability markers glycerophosphocholine and N-acetylaspartate in CM, indicative of gradual loss of cell viability [22].
• This finding correlated with a reduction of NAA levels, along with a rescue of the seizure phenotype [23].

Anatomical context of N-Acetyl-L-aspartic acid

• Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease [24].
• Previous magnetic resonance spectroscopy (MRS) studies have shown that N-acetylaspartate (NAA) is reduced not only in the ipsilateral but also in the contralateral hippocampus of many patients with mesial temporal lobe epilepsy (mTLE) [25].
• These data validate magnetic resonance spectroscopy measurements of N-acetylaspartate as an axon-specific monitor of central nervous system white matter in vivo [26].
• In the occipital lobe, NAA and ADP are 11.9 +/- 1.9mM and 32 +/- 12microM, respectively [27].
• The N-acetylaspartate signal, a putative marker of neuronal density, was markedly reduced in the forebrain [28].

Associations of N-Acetyl-L-aspartic acid with other chemical compounds

• Three days after unilateral bulbectomy there was a significant decrease in concentrations of N-acetylaspartylglutamate as well as aspartate, N-acetylaspartate, and gamma-aminobutyrate in the pyriform cortex of the side from which the olfactory bulb had been removed [29].
• When examined by magnetic resonance spectroscopic imaging, all patients showed a marked decrease of N-acetylaspartic acid, choline, and creatine in white matter only [30].
• Decreases in relative resonance intensities of N-acetylaspartate and creatine were seen both in and around the magnetic resonance imaging-detected lesions [31].
• Patients without collateral flow via any of these collaterals had decreased volume flow in the middle cerebral artery, decreased N-acetylaspartate/choline, and increased lactate/N-acetylaspartate, compared with the other patients [32].
• For the schizophrenia patients, the glutamine level in the left thalamus was found to be higher than normal, and there was a significant negative correlation between N-acetylaspartate level and duration of positive symptoms [33].

Gene context of N-Acetyl-L-aspartic acid

• Our success in preparing the recombinant ASPA in high purity should permit multiple lines of investigations to understand the pathogenic mechanisms of Canavan disease and the functional roles of NAA [34].
• Systemic administration of bFGF had significant neuroprotective effects as assessed by T2-weighted magnetic resonance imaging and measurements of n-acetylaspartate and lactate using chemical shift magnetic resonance imaging [35].
• Our preliminary results suggest that reduction in N-acetylaspartate/total creatine ratio may not be related to the MECP2 mutation [36].
• ASPA acts to hydrolyze N-acetylaspartate (NAA) into l-aspartate and acetate, but the connection between ASPA deficiency and the failure of proper CNS development is unclear [24].
• Reduced N-acetylaspartate levels in mice lacking aralar, a brain- and muscle-type mitochondrial aspartate-glutamate carrier [37].

Analytical, diagnostic and therapeutic context of N-Acetyl-L-aspartic acid

• We report a longitudinal study in which changes in the N-acetylaspartate to creatine resonance intensity ratio measured by brain proton magnetic resonance spectroscopy were used to follow the progression of brain pathology in 7 patients with multiple sclerosis over an 18-month period [38].
• We investigated the correlation between N-acetylaspartate (NAA) level and neuronal density in the hippocampal CA1 region of the brain after occlusion of both common carotid arteries for 5 minutes and reperfusion for 3 hours to 4 weeks in gerbils with and without ischemic preconditioning (tolerance) [5].
• The in vivo measurement of N-acetylaspartic acid in the brain by 1H magnetic resonance spectroscopy offers an additional noninvasive diagnostic test for establishing the diagnosis of Canavan's disease [39].
• In order to investigate N-acetylaspartate specificity for white matter axons, transected rat optic nerves were analyzed by high-performance liquid chromatography and immunohistochemistry [26].
• The main result of photic stimulation in patients with migraine with aura is the more consistent decrease (-14.61%) of the N-acetylaspartate (NAA) signal, which is significantly greater than that found in migraine patients without aura and control subjects [40].

References