**Background**
Glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system, playing a critical role in synaptic plasticity, learning, and memory. It exerts its effects by binding to various ionotropic and metabotropic glutamate receptors, including NMDA, AMPA, and mGlu receptors. Dysregulation of glutamatergic signaling is closely linked to various neurological conditions, where excessive glutamate can lead to excitotoxicity and neuronal death, while insufficient signaling may impair cognitive functions. Understanding the precise interaction between this amino acid and its receptors is essential for developing therapies for neurodegenerative diseases. In this context, we will introduce an excitatory amino acid neurotransmitter – L-Glutamic acid.
**Definition**
L-Glutamic acid is an agonist for all subtypes of glutamate receptors, including metabotropic and ionotropic receptors. According to the L-Glutamic acid technical information, it exhibits potent agonist activity with EC50 values ranging from 0.06 μM at human mGluR3 to 1.8 μM at rat NR1/NR2A receptors.
**In Vitro and In Vivo Studies**
The L-Glutamic acid biological activity has been extensively characterized across various models. In vitro, L-Glutamic acid (120, 500, 750, 1000 mg/dL) has been shown to reduce the harmful effects of lithium on the embryonic development of Xenopus laevis. Furthermore, in human neuroblastoma cell lines including SH-SY5Y, IMR-32, and SK-N-BE(2), L-Glutamic acid (2, 5, 10, 20 mM; 24-48 h) induces neuroexcitotoxicity, resulting in a dose-dependent reduction in cell viability.
L-Glutamic acid in vivo studies have demonstrated its dual role in toxicity and protection. In a Crv4 mice model, a single subcutaneous injection of L-Glutamic acid (3 g/kg) promoted the excitotoxic degeneration of retinal ganglion cells, reducing the number of Brn-3a+ RGCs by over 70%, an effect that was diminished in the absence of the mGlu1 receptor. Conversely, in a chlorpyrifos (CPF)-induced rat model, intraperitoneal administration of L-Glutamic acid (750 mg/kg) inhibited oxidative stress by increasing GSH levels and the activity of GSH-related enzymes. In conclusion, L-Glutamic acid is a versatile excitatory neurotransmitter and agonist used widely in the study of neurological diseases and excitotoxicity.
Keywords
L-Glutamic acid, 56-86-0, Endogenous Metabolite, iGluR, Ferroptosis, Apoptosis, Ionotropic glutamate receptors, NMDA, Agonist, SH-SY5Y, IMR-32, SK-N-BE(2), Neurotoxicity, Crv4 mice, Inhibitor
References
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