Glutamate ionotropic receptor NMDA type subunit 2C (GluN2C) (GluN2C)

The Glutamate ionotropic receptor NMDA type subunit 2C (GluN2C) is a specialized component of the N-methyl-D-aspartate (NMDA) receptor complex, primarily localized in the cerebellum, thalamus, and olfactory bulb [UniProt]. Unlike the more widely distributed GluN2A and GluN2B subunits, GluN2C-containing receptors possess unique biophysical properties, such as a lower sensitivity to magnesium block and slower deactivation kinetics, which allow them to mediate distinct forms of tonic and synaptic signaling [PubMed: 29445225]. These receptors are essential for regulating excitatory neurotransmission and have been implicated in the pathophysiology of various central nervous system disorders, including schizophrenia, bipolar disorder, and neurodevelopmental conditions [PubMed: 31430304]. From a therapeutic perspective, GluN2C is an attractive target for drug development, particularly through the use of positive allosteric modulators (PAMs) aimed at restoring NMDA receptor function in cognitive and social deficits [PubMed: 25143426]. While non-selective NMDA antagonists like memantine and ketamine interact with this subunit, their lack of specificity often results in broad side effects [StatPearls]. Selective modulation of GluN2C offers a potential strategy to influence specific brain circuits, such as the cerebello-thalamo-cortical pathway, with a potentially improved safety profile compared to pan-NMDA receptor modulators [PubMed: 29445225].

Other names

GRIN2CNMDAR2CNR2CGlutamate receptor ionotropic, NMDA 2C

Uncompetitive channel block, positive allosteric modulation, and co-agonist site activation