Glutamate-Induced Excitotoxicity and Its Impact on Neurodegenerative Diseases
Keywords:
Glutamate-Induced Excitotoxicity, Neurodegenerative Diseases, Neurotransmitter, Synaptic transmissionAbstract
Glutamate, the predominant excitatory neurotransmitter in the central nervous system, is crucial for normal brain function, including synaptic transmission, plasticity, learning, and memory. However, excessive activation of glutamate receptors can lead to excitotoxicity, a pathological process resulting in neuronal injury and death. Excitotoxicity is implicated in the pathogenesis of several major neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and multiple sclerosis (MS). In AD, amyloid-beta plaques and tau tangles disrupt glutamate homeostasis, leading to NMDA receptor overactivation and subsequent calcium overload. In PD, dopaminergic neuron degeneration enhances NMDA receptor sensitivity, exacerbating excitotoxic damage. ALS is characterized by impaired glutamate uptake due to EAAT2 dysfunction, leading to motor neuron death through NMDA and AMPA receptor overactivation. In HD, mutant huntingtin protein disrupts glutamate transporters and increases NMDA receptor activity, resulting in striatal neuronal loss.
How to cite this article:
Fernandes A, Rasiah A. Glutamate-
Induced Excitotoxicity and Its Impact on
Neurodegenerative Diseases. Int J Adv Res Pharm
Edu 2024; 6(1): 13-18.
References
Lau A, Tymianski M. Glutamate receptors, neurotoxicity
and neurodegeneration. Pflügers Archiv-European
Journal of Physiology. 2010 Jul;460:525-42.
Jakaria M, Park SY, Haque ME, Karthivashan G, Kim
IS, Ganesan P, Choi DK. Neurotoxic agent-induced
injury in neurodegenerative disease model: Focus
on involvement of glutamate receptors. Frontiers in
molecular neuroscience. 2018 Aug 29;11:307.
Zhang LN, Hao L, Wang HY, Su HN, Sun YJ, Yang XY, Che
B, Xue J, Gao ZB. Neuroprotective effect of resveratrol
against glutamate-induced excitotoxicity. Adv Clin Exp
Med. 2015 Jan 1;24(1):161-5.
Clark IA, Vissel B. Excess cerebral TNF causing
glutamate excitotoxicity rationalizes treatment of
neurodegenerative diseases and neurogenic pain by
anti-TNF agents. Journal of neuroinflammation. 2016
Dec;13:1-6.
Armada-Moreira A, Gomes JI, Pina CC, Savchak
OK, Gonçalves-Ribeiro J, Rei N, Pinto S, Morais TP,
Martins RS, Ribeiro FF, Sebastião AM. Going the extra
(synaptic) mile: excitotoxicity as the road toward
neurodegenerative diseases. Frontiers in cellular
neuroscience. 2020 Apr 24;14:90.
Mehta A, Prabhakar M, Kumar P, Deshmukh R,
Sharma PL. Excitotoxicity: bridge to various triggers
in neurodegenerative disorders. European journal of
pharmacology. 2013 Jan 5;698(1-3):6-18.
Iovino L, Tremblay ME, Civiero L. Glutamate-induced
excitotoxicity in Parkinson’s disease: The role of glial
cells. Journal of pharmacological sciences. 2020 Nov
;144(3):151-64.
Sheldon AL, Robinson MB. The role of glutamate
transporters in neurodegenerative diseases
and potential opportunities for intervention.
Neurochemistry international. 2007 Nov 1;51(6-7):333-
Dong XX, Wang Y, Qin ZH. Molecular mechanisms of
excitotoxicity and their relevance to pathogenesis of
neurodegenerative diseases. Acta Pharmacologica
Sinica. 2009 Apr;30(4):379-87.
Schubert D, Piasecki D. Oxidative glutamate toxicity
can be a component of the excitotoxicity cascade.
Journal of Neuroscience. 2001 Oct 1;21(19):7455-62.
Yu SP, Jiang MQ, Shim SS, Pourkhodadad S, Wei L.
Extrasynaptic NMDA receptors in acute and chronic
excitotoxicity: implications for preventive treatments
of ischemic stroke and late-onset Alzheimer’s disease.
Molecular Neurodegeneration. 2023 Jul 3;18(1):43.
Binvignat O, Olloquequi J. Excitotoxicity as a target
against neurodegenerative processes. Current
Pharmaceutical Design. 2020 Apr 1;26(12):1251-62.
Parsons MP, Raymond LA. Extrasynaptic NMDA
receptor involvement in central nervous system
disorders. Neuron. 2014 Apr 16;82(2):279-93.
Lai TW, Zhang S, Wang YT. Excitotoxicity and stroke:
identifying novel targets for neuroprotection. Progress
in neurobiology. 2014 Apr 1;115:157-88.
Schubert D, Piasecki D. Oxidative glutamate toxicity
can be a component of the excitotoxicity cascade.
Journal of Neuroscience. 2001 Oct 1;21(19):7455-62.
