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Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review
L-glutamate (L-Glu) is a nonessential amino acid, but an extensively utilised excitatory neurotransmitter with critical roles in normal brain function. Aberrant accumulation of L-Glu has been linked to neurotoxicity and neurodegeneration. To investigate this further, we systematically reviewed the l...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139234/ https://www.ncbi.nlm.nih.gov/pubmed/35624964 http://dx.doi.org/10.3390/brainsci12050577 |
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author | AL-Nasser, Maryam N. Mellor, Ian R. Carter, Wayne G. |
author_facet | AL-Nasser, Maryam N. Mellor, Ian R. Carter, Wayne G. |
author_sort | AL-Nasser, Maryam N. |
collection | PubMed |
description | L-glutamate (L-Glu) is a nonessential amino acid, but an extensively utilised excitatory neurotransmitter with critical roles in normal brain function. Aberrant accumulation of L-Glu has been linked to neurotoxicity and neurodegeneration. To investigate this further, we systematically reviewed the literature to evaluate the effects of L-Glu on neuronal viability linked to the pathogenesis and/or progression of neurodegenerative diseases (NDDs). A search in PubMed, Medline, Embase, and Web of Science Core Collection was conducted to retrieve studies that investigated an association between L-Glu and pathology for five NDDs: Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Together, 4060 studies were identified, of which 71 met eligibility criteria. Despite several inadequacies, including small sample size, employment of supraphysiological concentrations, and a range of administration routes, it was concluded that exposure to L-Glu in vitro or in vivo has multiple pathogenic mechanisms that influence neuronal viability. These mechanisms include oxidative stress, reduced antioxidant defence, neuroinflammation, altered neurotransmitter levels, protein accumulations, excitotoxicity, mitochondrial dysfunction, intracellular calcium level changes, and effects on neuronal histology, cognitive function, and animal behaviour. This implies that clinical and epidemiological studies are required to assess the potential neuronal harm arising from excessive intake of exogenous L-Glu. |
format | Online Article Text |
id | pubmed-9139234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91392342022-05-28 Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review AL-Nasser, Maryam N. Mellor, Ian R. Carter, Wayne G. Brain Sci Systematic Review L-glutamate (L-Glu) is a nonessential amino acid, but an extensively utilised excitatory neurotransmitter with critical roles in normal brain function. Aberrant accumulation of L-Glu has been linked to neurotoxicity and neurodegeneration. To investigate this further, we systematically reviewed the literature to evaluate the effects of L-Glu on neuronal viability linked to the pathogenesis and/or progression of neurodegenerative diseases (NDDs). A search in PubMed, Medline, Embase, and Web of Science Core Collection was conducted to retrieve studies that investigated an association between L-Glu and pathology for five NDDs: Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Together, 4060 studies were identified, of which 71 met eligibility criteria. Despite several inadequacies, including small sample size, employment of supraphysiological concentrations, and a range of administration routes, it was concluded that exposure to L-Glu in vitro or in vivo has multiple pathogenic mechanisms that influence neuronal viability. These mechanisms include oxidative stress, reduced antioxidant defence, neuroinflammation, altered neurotransmitter levels, protein accumulations, excitotoxicity, mitochondrial dysfunction, intracellular calcium level changes, and effects on neuronal histology, cognitive function, and animal behaviour. This implies that clinical and epidemiological studies are required to assess the potential neuronal harm arising from excessive intake of exogenous L-Glu. MDPI 2022-04-29 /pmc/articles/PMC9139234/ /pubmed/35624964 http://dx.doi.org/10.3390/brainsci12050577 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 | Systematic Review AL-Nasser, Maryam N. Mellor, Ian R. Carter, Wayne G. Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review |
title | Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review |
title_full | Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review |
title_fullStr | Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review |
title_full_unstemmed | Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review |
title_short | Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review |
title_sort | is l-glutamate toxic to neurons and thereby contributes to neuronal loss and neurodegeneration? a systematic review |
topic | Systematic Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139234/ https://www.ncbi.nlm.nih.gov/pubmed/35624964 http://dx.doi.org/10.3390/brainsci12050577 |
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