Glutamate ionotropic receptor NMDA type subunit 2D (GluN2D)

The Glutamate ionotropic receptor NMDA type subunit 2D (GluN2D) is a protein encoded by the GRIN2D gene that forms part of the heterotetrameric NMDA receptor complex, a primary mediator of excitatory neurotransmission in the mammalian brain (UniProt Q14957). GluN2D-containing receptors are distinguished by their unique kinetic properties, including low conductance and exceptionally slow deactivation rates, which allow for prolonged calcium signaling (Traynelis et al., 2010). While widely expressed during embryonic development, its expression in the adult brain becomes more restricted to specific areas such as the basal ganglia, thalamus, and brainstem (NCBI Gene 2906). Mutations in the GRIN2D gene are strongly associated with developmental and epileptic encephalopathy, while altered expression levels are implicated in the pathophysiology of schizophrenia and Parkinson's disease (Li et al., 2016). Therapeutic strategies targeting GluN2D aim to modulate synaptic excitability, with research focusing on subunit-selective negative allosteric modulators like DQP-1105 to treat seizure disorders or positive modulators for cognitive enhancement (Acker et al., 2011). However, drug development is challenged by the need for high selectivity to avoid the dissociative and cognitive side effects typically associated with broad-spectrum NMDA receptor antagonism.

Other names

GRIN2DNR2DNMDAR2DGlutamate receptor epsilon-4GluR epsilon 4

Negative allosteric modulation or non-competitive antagonism of the NMDA receptor complex to regulate ion flow and neuronal excitability (Traynelis et al., 2010).