Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.26 (
GSK
)
6,788
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Overactivation of N-methyl-D-aspartate (NMDA) receptors has been associated with neurodegenerative disorders such as Alzheimer's disease (AD), cerebral vascular disorders and amyotrophic lateral sclerosis (ALS). We have previously designed and synthesized a series of memantine nitrate and some of them have shown vessel dilatory effects and neuroprotective effects; however, the detailed mechanisms have not been elucidated. In this study, we further demonstrated that memantine nitrate-06 (MN-06), one of the novel compounds derived from memantine, possessed significant neuroprotective effects against glutamate-induced excitotoxicity in rat primary cerebellar granule neurons (CGNs). Pretreatment of MN-06 reversed the activation of GSK3b and the suppression of phosphorylated Akt induced by glutamate. In addition, the neuroprotective effects of MN-06 could be abolished by LY294002, the specific phosphatidylinositol 3-kinase (PI3-K) inhibitor. Ca
2+
imaging shown that pretreatment of MN-06 prevented Ca
2+
influx induced by glutamate. Moreover, MN-06 might inhibit the NMDA-mediated current by antagonizing
NDMA
receptors, which was further confirmed by molecular docking simulation. Taken together, MN-06 protected against glutamate-induced excitotoxicity by blocking calcium influx and attenuating PI3-K/Akt/
GSK
-3b pathway, indicating that MN-06 might be a potential drug for treating neurodegenerative disorders.
...
PMID:Multifunctional memantine nitrate significantly protects against glutamate-induced excitotoxicity via inhibiting calcium influx and attenuating PI3K/Akt/GSK3beta pathway. 3209
