Research Topic

Enzymes Regulating the Homeostasis of Agonists and Antagonists of the N-Methyl D-Aspartate Receptors

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N-Methyl D-aspartate receptors (NMDAR) are ligand-gated ion channels involved in numerous neurological functions, including memory, learning, and synaptic plasticity. Its main agonist is L-glutamate, produced by glutaminase, aminotransferase, and oxyprolinase. D-serine and glycine are co-agonists, with ...

N-Methyl D-aspartate receptors (NMDAR) are ligand-gated ion channels involved in numerous neurological functions, including memory, learning, and synaptic plasticity. Its main agonist is L-glutamate, produced by glutaminase, aminotransferase, and oxyprolinase. D-serine and glycine are co-agonists, with D-serine produced by serine racemase and glycine produced by L-serine degradation or direct synthesis. A metabolite of the kynurenine pathway, kynurenic acid (produced by kynurenine aminotransferase-II), acts as an antagonist whereas another metabolite of the same pathway, quinolinate, is a potent agonist. Other NMDAR ligands, such as magnesium and zinc ions, play regulatory roles.

High activity of NMDAR is associated with several neuropathologies, including Parkinson's, Alzheimer's, lateral amyotrophic sclerosis, and ischemia, whereas low activity is associated with schizophrenia. Presently, pharmacological treatment is based on ligands targeting NMDAR, and is endowed with severe side effects.

The focus of this Research Topic will be on the enzymes that are involved in the synthesis and degradation of the main agonists and antagonists of NMDAR, thus controlling their homeostasis. The understanding of the structure, dynamics, function, and regulation of these enzymes is the prerequisite for the development of drugs that allow for the fine-tuning of NMDAR activity.


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