Comprehensive Insight of Neurodegenerative Diseases and The Role of Neurotoxin Agents — Glutamate

The increased concentration of extracellular glutamate has been reported to play a key role in most of the neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease, even though its importance as an amino acid neurotransmitter in mammalian. Glutamate toxicity, which can be caus...

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Main Authors: Hui-Min Yap, Kwan-Liang Lye, Loh Teng-Hern Tan
Format: Article
Language:English
Published: HH Publisher 2020-04-01
Series:Progress in Microbes and Molecular Biology
Online Access:https://journals.hh-publisher.com/index.php/pmmb/article/view/140
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author Hui-Min Yap
Kwan-Liang Lye
Loh Teng-Hern Tan
author_facet Hui-Min Yap
Kwan-Liang Lye
Loh Teng-Hern Tan
author_sort Hui-Min Yap
collection DOAJ
description The increased concentration of extracellular glutamate has been reported to play a key role in most of the neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease, even though its importance as an amino acid neurotransmitter in mammalian. Glutamate toxicity, which can be caused by excessive intake of monosodium glutamate (MSG), is the major contributor to pathological neuronal cell death. It causes neuronal dysfunction and degeneration in the central nervous system (CNS). Glutamate neurotoxicity can be categorized into two forms, which are receptor-mediated glutamate excitotoxicity and non-receptor mediated glutamate oxidative toxicity. The receptor-mediated glutamate excitotoxicity involved excessive stimulation of glutamate receptors (GluRs) which lead to excessive ion calcium (Ca2+) influx and activates a cell death cascade involving the accumulation of mitochondrially generated reactive oxygen species (ROS). Studies showed excessive extracellular glutamate leads to nerve cell death via the activation of N-methyl-Daspartate (NMDA) receptors in the cases of trauma or stroke. Whereas non-receptor mediated oxidative toxicity involved the breakdown of the cystine/glutamate antiporter (xc - ) mechanism, which leads to the depletion of glutathione (GSH) and causes oxidative stress and cell death. The cystine/glutamate antiporter couples the import of cystine to the export of glutamate. The increased concentration of extracellular glutamate could inhibit the uptake of cystine, which is required for the synthesis of the intracellular antioxidant GSH. GSH plays an important role in the disposal of peroxides by brain cells and in the protection against ROS. Depletion of GSH renders the cell to oxidative stress and ultimately leading to cell death. This article aims to provide a comprehensive review of neurodegenerative diseases and the role of neurotoxin agents, glutamate in these diseases.
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spelling doaj-art-126ad8156cc44728b328dc0347f1b4982025-02-04T08:37:07ZengHH PublisherProgress in Microbes and Molecular Biology2637-10492020-04-013110.36877/pmmb.a0000070Comprehensive Insight of Neurodegenerative Diseases and The Role of Neurotoxin Agents — GlutamateHui-Min YapKwan-Liang LyeLoh Teng-Hern TanThe increased concentration of extracellular glutamate has been reported to play a key role in most of the neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease, even though its importance as an amino acid neurotransmitter in mammalian. Glutamate toxicity, which can be caused by excessive intake of monosodium glutamate (MSG), is the major contributor to pathological neuronal cell death. It causes neuronal dysfunction and degeneration in the central nervous system (CNS). Glutamate neurotoxicity can be categorized into two forms, which are receptor-mediated glutamate excitotoxicity and non-receptor mediated glutamate oxidative toxicity. The receptor-mediated glutamate excitotoxicity involved excessive stimulation of glutamate receptors (GluRs) which lead to excessive ion calcium (Ca2+) influx and activates a cell death cascade involving the accumulation of mitochondrially generated reactive oxygen species (ROS). Studies showed excessive extracellular glutamate leads to nerve cell death via the activation of N-methyl-Daspartate (NMDA) receptors in the cases of trauma or stroke. Whereas non-receptor mediated oxidative toxicity involved the breakdown of the cystine/glutamate antiporter (xc - ) mechanism, which leads to the depletion of glutathione (GSH) and causes oxidative stress and cell death. The cystine/glutamate antiporter couples the import of cystine to the export of glutamate. The increased concentration of extracellular glutamate could inhibit the uptake of cystine, which is required for the synthesis of the intracellular antioxidant GSH. GSH plays an important role in the disposal of peroxides by brain cells and in the protection against ROS. Depletion of GSH renders the cell to oxidative stress and ultimately leading to cell death. This article aims to provide a comprehensive review of neurodegenerative diseases and the role of neurotoxin agents, glutamate in these diseases.https://journals.hh-publisher.com/index.php/pmmb/article/view/140
spellingShingle Hui-Min Yap
Kwan-Liang Lye
Loh Teng-Hern Tan
Comprehensive Insight of Neurodegenerative Diseases and The Role of Neurotoxin Agents — Glutamate
Progress in Microbes and Molecular Biology
title Comprehensive Insight of Neurodegenerative Diseases and The Role of Neurotoxin Agents — Glutamate
title_full Comprehensive Insight of Neurodegenerative Diseases and The Role of Neurotoxin Agents — Glutamate
title_fullStr Comprehensive Insight of Neurodegenerative Diseases and The Role of Neurotoxin Agents — Glutamate
title_full_unstemmed Comprehensive Insight of Neurodegenerative Diseases and The Role of Neurotoxin Agents — Glutamate
title_short Comprehensive Insight of Neurodegenerative Diseases and The Role of Neurotoxin Agents — Glutamate
title_sort comprehensive insight of neurodegenerative diseases and the role of neurotoxin agents glutamate
url https://journals.hh-publisher.com/index.php/pmmb/article/view/140
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AT kwanlianglye comprehensiveinsightofneurodegenerativediseasesandtheroleofneurotoxinagentsglutamate
AT lohtengherntan comprehensiveinsightofneurodegenerativediseasesandtheroleofneurotoxinagentsglutamate