Cargando…

N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

N-acetyl-aspartyl-glutamate (NAAG) is the most abundant dipeptide in the brain, where it acts as a neuromodulator of glutamatergic synapses by activating presynaptic metabotropic glutamate receptor 3 (mGluR3). Recent data suggest that NAAG is selectively localized to postsynaptic dendrites in glutam...

Descripción completa

Detalles Bibliográficos
Autores principales: Morland, Cecilie, Nordengen, Kaja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836185/
https://www.ncbi.nlm.nih.gov/pubmed/35163193
http://dx.doi.org/10.3390/ijms23031268
_version_ 1784649615221456896
author Morland, Cecilie
Nordengen, Kaja
author_facet Morland, Cecilie
Nordengen, Kaja
author_sort Morland, Cecilie
collection PubMed
description N-acetyl-aspartyl-glutamate (NAAG) is the most abundant dipeptide in the brain, where it acts as a neuromodulator of glutamatergic synapses by activating presynaptic metabotropic glutamate receptor 3 (mGluR3). Recent data suggest that NAAG is selectively localized to postsynaptic dendrites in glutamatergic synapses and that it works as a retrograde neurotransmitter. NAAG is released in response to glutamate and provides the postsynaptic neuron with a feedback mechanisms to inhibit excessive glutamate signaling. A key regulator of synaptically available NAAG is rapid degradation by the extracellular enzyme glutamate carboxypeptidase II (GCPII). Increasing endogenous NAAG—for instance by inhibiting GCPII—is a promising treatment option for many brain disorders where glutamatergic excitotoxicity plays a role. The main effect of NAAG occurs through increased mGluR3 activation and thereby reduced glutamate release. In the present review, we summarize the transmitter role of NAAG and discuss the involvement of NAAG in normal brain physiology. We further present the suggested roles of NAAG in various neurological and psychiatric diseases and discuss the therapeutic potential of strategies aiming to enhance NAAG levels.
format Online
Article
Text
id pubmed-8836185
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88361852022-02-12 N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease Morland, Cecilie Nordengen, Kaja Int J Mol Sci Review N-acetyl-aspartyl-glutamate (NAAG) is the most abundant dipeptide in the brain, where it acts as a neuromodulator of glutamatergic synapses by activating presynaptic metabotropic glutamate receptor 3 (mGluR3). Recent data suggest that NAAG is selectively localized to postsynaptic dendrites in glutamatergic synapses and that it works as a retrograde neurotransmitter. NAAG is released in response to glutamate and provides the postsynaptic neuron with a feedback mechanisms to inhibit excessive glutamate signaling. A key regulator of synaptically available NAAG is rapid degradation by the extracellular enzyme glutamate carboxypeptidase II (GCPII). Increasing endogenous NAAG—for instance by inhibiting GCPII—is a promising treatment option for many brain disorders where glutamatergic excitotoxicity plays a role. The main effect of NAAG occurs through increased mGluR3 activation and thereby reduced glutamate release. In the present review, we summarize the transmitter role of NAAG and discuss the involvement of NAAG in normal brain physiology. We further present the suggested roles of NAAG in various neurological and psychiatric diseases and discuss the therapeutic potential of strategies aiming to enhance NAAG levels. MDPI 2022-01-23 /pmc/articles/PMC8836185/ /pubmed/35163193 http://dx.doi.org/10.3390/ijms23031268 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Morland, Cecilie
Nordengen, Kaja
N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease
title N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease
title_full N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease
title_fullStr N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease
title_full_unstemmed N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease
title_short N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease
title_sort n-acetyl-aspartyl-glutamate in brain health and disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836185/
https://www.ncbi.nlm.nih.gov/pubmed/35163193
http://dx.doi.org/10.3390/ijms23031268
work_keys_str_mv AT morlandcecilie nacetylaspartylglutamateinbrainhealthanddisease
AT nordengenkaja nacetylaspartylglutamateinbrainhealthanddisease