1.Blockade of N-acetylaspartylglutamate peptidases: a novel protective strategy for brain injuries and neurological disorders.
Zhong C;Luo Q;Jiang J Int J Neurosci. 2014 Dec;124(12):867-73. doi: 10.3109/00207454.2014.890935. Epub 2014 Feb 13.
The peptide neurotransmitter N-acetylaspartylglutamate (NAAG) is reported to suppress glutamate release mainly through selective activation of presynaptic Group II metabotropic glutamate receptor subtype 3 (mGluR3). Therefore, strategies of inhibition of NAAG peptidases and subsequent NAAG hydrolysis to elevate levels of NAAG could reduce glutamate release under pathological conditions and be neuroprotective by attenuating excitotoxic cell injury. A series of potent inhibitors of NAAG peptidases has been synthesized and demonstrated efficacy in experimental models of ischemic-hypoxic brain injury, traumatic brain injury, inflammatory pain, diabetic neuropathy, amyotrophic lateral sclerosis and phencyclidine-induced schizophrenia-like behaviors. The excessive glutamatergic transmission has been implicated in all of these neurological disorders. Thus, blockade of NAAG peptidases may augment an endogenous protective mechanism and afford neuroprotection in the brain. This review aims to summarize and provide insight into the current understanding of the novel neuroprotective strategy based on limiting glutamate excitotoxicity for a wide variety of brain injuries and neurological disorders.
2.Distribution of N-acetylaspartate, N-acetylaspartylglutamate, free glutamate and aspartate following complete mesencephalic transection in rat neuraxis.
D'Arcangelo P;Brancati A Neurosci Lett. 1990 Jun 22;114(1):82-8.
The distribution of N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), free glutamate (Glu) and aspartate (Asp) was studied in the neuraxis of rats 48 h after complete transection of brain stem at the intercollicular level. NAA remained unchanged above the transection level but decreased in the neur-axis segments caudal to the lesion. Glu was strongly depressed both in the segments rostral to the transection and in the ones caudal to it. No significant change was found for NAAG and Asp. These findings are consistent with the hypothesis that NAA may be involved in neurotransmission processes and provide further evidence for Glu as transmitter of descending and ascending pathways. In addition, the data obtained do not suggest a direct metabolic or functional relationship between NAA and NAAG nor between these N-acetylderivatives and free Glu and Asp.
3.The impact of acute and short-term methamphetamine abstinence on brain metabolites: A proton magnetic resonance spectroscopy chemical shift imaging study.
Burger A;Brooks SJ;Stein DJ;Howells FM Drug Alcohol Depend. 2018 Apr 1;185:226-237. doi: 10.1016/j.drugalcdep.2017.11.029. Epub 2018 Feb 22.
BACKGROUND: ;Abuse of methamphetamine (MA) is a global health concern. Previous ;1;H-MRS studies have found that, with methamphetamine abstinence (MAA), there are changes in n-acetyl-aspartate (NAA/Cr), myo-inositol (mI/Cr), choline (Cho/Cr and Cho/NAA), and glutamate with glutamine (Glx) metabolites. Limited studies have investigated the effect of acute MAA, and acute-to-short-term MAA on brain metabolites.;METHODS: ;Adults with chronic MA dependence (n = 31) and healthy controls (n = 22) were recruited. Two-dimensional chemical shift ;1;H-MRS imaging (TR2000 ms, TE30 ms) slice was performed and included voxels in bilateral anterior-cingulate (ACC), frontal-white-matter (FWM), and dorsolateral-prefrontal-cortices (DLPFC). Control participants were scanned once. The MA group was scanned twice, with acute (1.5 ± 0.6 weeks, n = 31) and short-term MAA (5.1 ± 0.8 weeks, n = 22). The change in ;1;H-MRS metabolites over time (n = 19) was also investigated. Standard ;1;H-MRS metabolites are reported relative to Cr + PCr.;RESULTS: ;Acute MAA showed lower n-acetyl-aspartate (NAA) and n-acetyl-aspartate with n-acetyl-aspartyl-glutamate (NAA + NAAG) in left DLPFC, and glycerophosphocholine with phosphocholine (GPC + PCh) in left FWM.
