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.

Abstract

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.

Citation

Al-Nasser, M. N., Mellor, I. R., & Carter, W. G. (2022). Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review. Brain Sciences, 12(5), Article 577. https://doi.org/10.3390/brainsci12050577

• Journal Article Type: Review
• Acceptance Date: Apr 26, 2022
• Online Publication Date: Apr 29, 2022
• Publication Date: Apr 29, 2022
• Deposit Date: Apr 27, 2022
• Publicly Available Date: Apr 29, 2022
• Journal: Brain Sciences
• Electronic ISSN: 2076-3425
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 5
• Article Number: 577
• DOI: https://doi.org/10.3390/brainsci12050577
• Keywords: excitotoxicity; L-glutamate; mitochondrial dysfunction; neurodegeneration; neuroin-29 flammation; oxidative stress; protein aggregation
• Public URL: https://nottingham-repository.worktribe.com/output/7835654
• Publisher URL: https://www.mdpi.com/2076-3425/12/5/577