Potential protective roles of phytochemicals on glutamate-induced neurotoxicity: A review

Document Type : Review Article


1 Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

2 Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

4 Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran


Glutamate, as an essential neurotransmitter, has been thought to have different roles in the central nervous system (CNS), including nerve regeneration, synaptogenesis, and neurogenesis. Excessive glutamate causes an up-regulation of the multiple signaling pathways, including phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), Akt/mammalian target of rapamycin (mTOR) protein, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)1/2, and autophagy that are involved in neurodegenerative diseases pathophysiology. There are numerous findings on curcumin, astaxanthin, thymoquinone, and berberine, as natural products, which have outstanding effects in cell signaling far beyond their anti-oxidant activity, considering as a potential therapeutic target for glutamate excitotoxicity. Herein, we address the role of glutamate as a potential target in neurodegenerative diseases and discuss the protective effects of certain phytochemicals on glutamate-induced neurotoxicity.


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