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Amyloid-beta peptide (Abeta) plays a causal role in the pathogenesis of Alzheimer's disease (AD). To elucidate the mechanisms underlying the over-activation of NMDA receptors in AD, we investigated the alteration of NR2A tyrosine phosphorylation after intracerebroventricular infusion of Abeta25-35 oligomers. Abeta25-35 treatment resulted in the elevated(More)
Oligomeric amyloid-β peptide (Aβ) has been found to be associated with the pathogenesis of Alzheimer's disease (AD). Numerous studies have reported Aβ neurotoxicity, but the underlying molecular mechanisms remain to be fully illuminated. In the present study, we investigated the Aβ-induced activation and regulation of P38MAPKs in rat hippocampus in vivo.(More)
Amyloid-beta peptide (Abeta) has been implicated in the etiopathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms underlying Abeta neurotoxicity remain to be elucidated. This study showed that Abeta treatment resulted in the increased phosphorylation (activation) of MLK3, MKK7, and JNK3 in cultured cortical neurons, which characterized(More)
Recent studies have indicated that tyrosine phosphorylation of NMDA receptor subunit 2A (NR2A) by Src family kinases (Src, Fyn, etc.) up-regulates NMDA receptors activity and postsynaptic density protein 95 kDa (PSD95) may mediate the regulation. To investigate whether the above processes are involved in brain ischemia-induced enhancement of NMDA receptors(More)
The effects of suppression of postsynaptic density protein 95 (PSD-95) expression on the increased tyrosine phosphorylation of N-methyl-D-aspartate receptor subunit NR2A and interactions of Src and Fyn with NR2A after brain ischemia were investigated by immunoprecipitation and immunoblotting. Transient (15 min) brain ischemia was induced by the four-vessel(More)
AIMS Src family protein tyrosine kinases (SrcPTKs) have been implicated in the pathogenesis of brain ischemia and Alzheimer's disease (AD). In this study, we investigated whether Src and Fyn kinases, two major members of SrcPTKs in the brain, have distinct roles in the oxygen and glucose deprivation (OGD) and amyloid-β peptide (Aβ)-induced neuronal(More)
Previous studies have shown that KA receptor subunit GluR6 mediated c-Jun N-terminal protein kinase (JNK) signaling is involved in global ischemia injury. Our present study indicates that focal ischemic brain insult on rat middle cerebral artery occlusion (MACo) model enhances the assembly of the GluR6-PSD95-MLK3 module and facilitates the phosphorylation(More)
Amyloid-β peptide (Aβ) has been implicated in the development of Alzheimer's disease (AD), but the underlying molecular mechanisms remain unclear. The present study explores the proapoptosis signaling evoked by N-methyl-D-aspartate (NMDA) receptors in Aβ neurotoxicity. Oligomeric Aβ25-35 incubation resulted in significant apoptosis of neuronal SH-SY5Y(More)
The activation of postsynaptic N-methyl-d-aspartate (NMDA) receptors is required for long-term potentiation (LTP) of synaptic transmission. Postsynaptic density 95 (PSD-95) serves as a scaffold protein that tethers NMDA receptor subunits, kinases, and signal molecules. Our previous study proves that PSD-95 is a substrate of Src/Fyn and identifies Y523 on(More)
S-nitrosoglutathione (GSNO) has been reported to protect against ischemic brain injury, however, the underlying mechanisms remain to be elucidated. In the present study, we aimed to investigate the effects of GSNO pre-treatment on the S-nitrosylation of Fas and subsequent events in the Fas pathway, and reveal the correlation between Fas S-nitrosylation and(More)