NMDA receptor–postsynaptic density protein 95 complex (NMDA receptor–PSD-95 complex)

The **NMDA receptor–postsynaptic density protein 95 (PSD-95) complex** is a key macromolecular assembly at excitatory synapses in the central nervous system. It consists of **NMDA receptors**—glutamate-gated ion channels critical for synaptic transmission, plasticity, and learning—and the scaffold protein **PSD-95**, which anchors these receptors to the postsynaptic membrane via PDZ domain interactions, especially with the GluN2 subunit of NMDARs[3][2][1][4]. PSD-95 stabilizes NMDA receptors at synapses, regulates their trafficking and surface expression, and organizes associated signaling and structural proteins[1][2][4]. Abnormalities in the NMDA receptor–PSD-95 complex are associated with multiple neurological and psychiatric diseases, making it a promising therapeutic target. Drugs targeting this complex aim to modulate excitatory neurotransmission, synaptic plasticity, or pathologically enhanced signaling without broadly inhibiting normal synaptic transmission[1][2][3][4].

Other names

NMDA receptor–PSD95 complexNMDAR–PSD-95 complexN-methyl-D-aspartate receptor–postsynaptic density-95 complex

NMDA receptor antagonists block excitatory neurotransmission at the receptor, reducing calcium influx and excitotoxicity. Disruption of NMDA receptor–PSD-95 interaction with peptide inhibitors or small molecules (aiming to reduce pathological signaling without compromising physiological function).