Promising targets of cell death signaling of NR2B receptor subunit in stroke pathogenesis

Stroke is an acute cerebrovascular disease caused by acute brain artery bursting or cerebral embolism that leads to neuronal death and severe dysfunction of synaptic transmission. Neuronal damage after stroke remains a major cause of morbidity and mortality worldwide and affects 795 000 of lives every year in United States. However, effective treatments remain lacking, which makes the identification of new therapeutic targets a matter of great importance. N-methyl-D-aspartate glutamate (NMDA) receptor is important both in the normal synaptic transmission and in the neuronal death after stroke. Accumulated evidences show NMDA receptor downstream effectors, such as PSD-95, DAPK1, and ERK, had been revealed to be linked with neuronal damage. Based on our recent studies, we review the promising targets of the NMDA receptor downstream signaling involved in stroke treatment. This review will provide the concept of NR2B downstream signaling in neuronal death after stroke and provide evidences for developing better NMDAR-based therapeutics by targeting downstream proteins.