Abstract
N-Methyl-d-aspartate receptors (NMDARs) are broadly distributed in the central nervous system (CNS), where they mediate excitatory signaling. NMDAR-mediated neurotransmission (NMDARMN) is the molecular engine of learning, memory and cognition, which are the basis for high cortical function. NMDARMN is also critically involved in the development and plasticity of CNS. Due to its essential and critical role, either over- or under-activation of NMDARMN can contribute substantially to the development of CNS disorders. The involvement of NMDARMN has been demonstrated in a variety of CNS disorders, including schizophrenia, depression, posttraumatic stress disorder, aging, mild cognitive impairment and Alzheimer's dementia, amyotrophic lateral sclerosis, and anti-NMDAR encephalitis. Several targets to "correct" or "reset" the NMDARMN in these CNS disorders have been identified and confirmed. With analogy to aminergic treatments, these targets include the glycine/d-serine co-agonist site, channel ionophore, glycine transporter-1, and d-amino acid oxidase. It is still early days in terms of developing novel therapeutics targeting the NMDAR. However, agents modulating NMDARMN hold promise as the next generation of CNS therapeutics.
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