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NMDAR

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. The involvement of NMDARMN has been demonstrated in a variety of CNS disorders, including schizophrenia, depression, posttraumatic stress disorder, aging, mild cognitive impairment (MCI) and Alzheimer’s dementia, attention deficit hyperactivity disorder, amyotrophic lateral sclerosis, and anti-NMDAR encephalitis. “Correction” or “resetting” the NMDARMN in these CNS disorders is a potential therapeutic approach. NMDAR distinguishes itself in two ways.
First, it is both ligand-gated and voltage-dependent; second, it requires co-activation by two agonists: glutamate or aspartate and either D-serine or glycine. Most NMDAR heterotetramers are composed of two NR1 and two NR2 subunits. Activation of NMDAR requires binding of both glutamate/aspatate to the NR2 subunit and its co-agonist, glycine/D-serine, to the NR1 subunit. D-serine/glycine binding is not only necessary for receptor activation; it also increases the affinity of the receptor for glutamate and modulates receptor function by decreasing receptor desensitization while promoting receptor turnover via internalization.

References

1.Tsai GE. Adv Pharmacol. 2016;76:257–309.

Membrane Transporter/Ion Channel

AMPK(52) ASBT Transporter(6) BCRP(9) Beta Amyloid(26) Carbonic Anhydrase(25) Chloride Channel(29) CRAC Channel(3) CRM1(4) Exportin-1(5) FABP(4) GAT(63) GLUT(5) Glutamate Transporter(1) GlyT(10) HCN Channel(4) iGluR(33) Monoamine Transporter(19) Monocarboxylate Transporter(7) MTP(1) nAChR(5) NADPH(25) Na-K-ATPase(1) NKCC(4) NMDAR(45) OCT(4) Other Targets(13) P2X Receptor(16) P-glycoprotein(10) Potassium Channel(0) Proton Pump(33) Sodium Channel(103) TRP/TRPV Channel(92) URAT1(1)