Neurodegeneration is the pathophysiological basis for permanent neurological disabilities in multiple sclerosis (MS); thus neuroprotection is emerging as a therapeutic approach in MS research. Modulation of excitotoxicity by inhibition of NMDARs has been suggested for neuroprotection, but selective antagonisation of the NR2B subtype of these receptors, a subtype believed to play a more pivotal ...

neurodegeneration is the pathophysiological basis for permanent neurological disabilities in multiple sclerosis (ms); thus neuroprotection is emerging as a therapeutic approach in ms research. modulation of excitotoxicity by inhibition of nmdars has been suggested for neuroprotection, but selective antagonisation of the nr2b subtype of these receptors, a subtype believed to play a more pivotal ...

The N-methyl-D-aspartate (NMDA) receptor NR2B subunit on neurons in the anterior cingulate cortex (ACC) is implicated in the affective response to noxious stimuli. Selectively silencing this NR2B subunit in ACC neurons could therefore alleviate pain-related aversion. However, to date, there is no optimal approach to selectively silence the NR2B gene in ACC neurons. In the present study, we cons...

Transgenic overexpression of NMDA NR2B receptors in forebrain regions increased behavioral responses to persistent inflammatory pain. However, it is not known whether inflammation leads to the upregulation of NR2B receptors in these regions. Here, we show that peripheral inflammation increased the expression of NMDA NR2B receptors and NR2B receptor-mediated synaptic currents in the anterior cin...

NMDA receptors (NMDARs) are critical mediators of activity-dependent synaptic plasticity, but the differential roles of NR2A- versus NR2B-containing NMDARs have been controversial. Here, we investigate the roles of NR2A and NR2B in long-term potentiation (LTP) in organotypic hippocampal slice cultures using RNA interference (RNAi) and overexpression, to complement pharmacological approaches. In...

The NR2 subunit composition of NMDA receptors (NMDARs) varies during development, and this change is important in NMDAR-dependent signaling. In particular, synaptic NMDAR switch from containing mostly NR2B subunit to a mixture of NR2B and NR2A subunits. The pathways by which neurons differentially traffic NR2A- and NR2B-containing NMDARs are poorly understood. Using single-particle and -molecul...

N-methyl-D-aspartate (NMDA) receptors constitute a major subtype of glutamate receptors at extrasynaptic sites that link multiple intracellular catabolic processes responsible for irreversible neuronal death. Here, we report that cerebral ischemia recruits death-associated protein kinase 1 (DAPK1) into the NMDA receptor NR2B protein complex in the cortex of adult mice. DAPK1 directly binds with...

We constructed a water-soluble lipopolymer (WSLP) as a nonviral gene carrier to deliver siRNA targeting NR2B. The cytotoxicity and serum stability of WSLP loaded with siRNA were evaluated, and the knockdown efficiency of WSLP/NR2B-siRNA in PC12 cells was examined. The results showed that WSLP could protect the loading siRNAs from enzymatic degradation in serum and exhibit low cytotoxicity to ce...

N-methyl-D-aspartate (NMDA) receptors (NMDARs) play a central role in development, synaptic plasticity, and neurological disease. NMDAR subunit composition defines their biophysical properties and downstream signaling. Casein kinase 2 (CK2) phosphorylates the NR2B subunit within its PDZ-binding domain; however, the consequences for NMDAR localization and function are unclear. Here we show that ...

Kinesin superfamily motor protein 17 (KIF17) is a candidate transporter of N-methyl-D-aspartate (NMDA) receptor subunit 2B (NR2B). Disruption of the murine kif17 gene inhibits NR2B transport, accompanied by decreased transcription of nr2b, resulting in a loss of synaptic NR2B. In kif17(-/-) hippocampal neurons, the NR2A level is also decreased because of accelerated ubiquitin-proteasome system-...