[1][2] In contrast to synaptic NMDA receptors that promote acquired neuroprotection and synaptic plasticity, extrasynaptic NMDA receptors are coupled to activation of death-signaling pathways.
[3] Extrasynaptic NMDA receptors are responsible for initiating excitotoxicity and have been implicated in the etiology of neurodegenerative diseases, including stroke, Huntington’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis (ALS).
[4][5][6][7][8] Extrasynaptic NMDA receptors form a death signaling complex with the transient receptor potential cation channel subfamily M member 4 (TRPM4).
The NMDAR/TRPM4 complex is considered central to glutamate excitotoxicity.
In mouse disease models, interface inhibitors protect against stroke induced brain damage and retinal ganglion cell degeneration.