Excitatory glutamatergic neurotransmission via N-methyl-significant for synaptic plasticity as well as endurance of neurons. However, extreme NMDAR activity causes excitotoxicity and initiates cell death, underlying a potential mechanism of neurodegeneration occurred in Alzheimer’s disease (AD). Studies suggest that the distinct outcomes of NMDAR-mediated responses are induced by receptor behavior, followed by various signaling pathways. The activation of synaptic NMDARs initiates plasticity and stimulates cell survival. In contrast, the activation of extrasynaptic NMDARs promotes cell death and thus contributes to the etiology of AD, which can be blocked by an AD drug - memantine, an NMDAR antagonist that selectively blocks the function of extrasynaptic NMDARs.
