N-methyl-D-aspartate receptor GluN2 subunit (GluN2) (GluN2)

The N-methyl-D-aspartate (NMDA) receptor GluN2 subunit is a critical component of the heterotetrameric NMDA receptor complex, which functions as a glutamate-gated cation channel in the central nervous system (UniProt P35436, P41231). These subunits (GluN2A, GluN2B, GluN2C, and GluN2D) contain the primary binding site for the excitatory neurotransmitter glutamate and are essential for the receptor's high permeability to calcium ions and its voltage-dependent magnesium block (PubMed: 25339580). Biologically, GluN2-containing receptors mediate synaptic plasticity, including long-term potentiation and depression, which are the cellular foundations of learning and memory (StatPearls: NMDA Receptor). Dysregulation of GluN2 subunits is implicated in a wide range of neurological and psychiatric disorders, such as Alzheimer's disease, where overactivation leads to excitotoxicity, and major depressive disorder, where NMDA modulation provides rapid antidepressant effects (PubMed: 30103115). Pharmacological targeting of these subunits includes uncompetitive channel blockers like memantine for dementia and GluN2B-selective negative allosteric modulators for mood disorders (PubChem: Memantine). Balancing the modulation of these receptors is a significant therapeutic challenge due to their dual role in essential cognitive functions and pathological neurotoxicity (PubMed: 29958029).

Other names

Glutamate receptor ionotropic NMDA 2NR2 subunitGRIN2NMDA receptor subunit 2Glutamate [NMDA] receptor subunit epsilon

Non-competitive antagonism, uncompetitive channel blocking, negative allosteric modulation, and positive allosteric modulation (PubMed: 25339580, PubChem: Memantine).