Protein kinase B (PKB, or Akt), a downstream effector of phosphatidylinositol 3-kinase (PI-3-K), can play a critical role in regulating neuronal survival. Among known targets of PKB, glycogen synthase kinase-3 (GSK-3) is inhibited by PKB-mediated phosphorylation. Recent studies implicate GSK-3 as a physiologically relevant principal regulatory target of the PI-3-K/PKB survival pathway. Here we show that SB-216763 and SB-415286, selective small molecule inhibitors of GSK-3, protected cultured rat cerebellar granule neurons and hippocampal neurons against excitotoxicity mediated by NMDA and non-NMDA receptor agonists. Treatment with SB-216763 and SB-415286 was optimal when initiated 6-7 days before excitotoxin exposure. As GSK-3 can modulate transcriptional events, these results may provide insight into the identification of new neuroprotective targets.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/00001756-200308060-00012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Expanding therapeutic options for Pompe disease: a new small molecule inhibitor of glycogen synthase 1 (GYS1) shows preclinical promise in Pompe disease.
Ann Transl Med
December 2024
Division of Medical Genetics, Duke University Medical Center, Durham, NC, USA.
Anti-inflammatory effects of water-dispersible hesperetin on endotoxin-induced uveitis in rats involving the nuclear factor κB and Wnt/β-catenin signaling pathways.
J Vet Med Sci
January 2025
Department of Small Animal Internal Medicine II, School of Veterinary Medicine, Kitasato University.
This study investigated the anti-inflammatory effects of water-dispersible hesperetin (WD-Hpt) in an endotoxin-induced uveitis (EIU) rat model. The rats were orally administered 10, 25, or 50 mg/kg WD-Hpt immediately after lipopolysaccharide (LPS) injection at the concentration of 200 μg. Clinical scores, cellular inflammation, the aqueous humor (ApH) protein concentration, as well as the levels of tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) in AqH, and histopathological grades were assessed.
View Article and Find Full Text PDFGlycogen synthase kinase-3ß inhibitor use and prostate cancer incidence in Manitoba, Canada: A population-based nested case-control study.
Cancer Epidemiol
January 2025
Vaccine and Drug Evaluation Centre, Department of Community Health Sciences, University of Manitoba, S108-750 Bannatyne Avenue, Winnipeg, MB R3E 0W2, Canada; College of Pharmacy, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB R3E 0T5, Canada.
Background: Little is known on the effect of glycogen synthase kinase-3ß inhibitors (GSK3Is), as a class, on prostate cancer (PC). We aimed to study this in the Canadian province of Manitoba, because mixed results have been reported on the effect of valproate.
Methods: We conducted a nested case-control study among cancer-free Manitobans with ≥ 5 years of medical history in which we matched all men 40 years or older diagnosed with PC between 2000 and 2018 (N = 11,189) on period, age, length of available drug information to cancer-free controls (N = 55,728).
Adrenomedullin 2 attenuates anxiety-like behaviors by increasing IGF-II in amygdala and re-establishing blood-brain barrier.
Transl Psychiatry
January 2025
Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Anxiety disorder, a prevalent mental health issue, is one of the leading causes of disability worldwide. Damage to the blood-brain barrier (BBB) is implicated in anxiety, but its regulatory mechanisms remain unclear. Herein, we show that adrenomedullin 2 (ADM2), a novel angiogenic growth factor, alleviates autistic and anxiety-like behaviors in mice.
View Article and Find Full Text PDFRemimazolam Suppresses Oxidative Stress and Apoptosis in Cerebral Ischemia/Reperfusion Injury by Regulating AKT/GSK-3β/NRF2 Pathway.
Drug Des Devel Ther
January 2025
Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
Introduction: The mechanism of remimazolam, a benzodiazepine that activates γ-aminobutyric acid a (GABAa) receptors, in cerebral ischemia/reperfusion (I/R) injury is not well understood. Therefore, we explored whether remimazolam activates protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β)/nuclear factor erythroid 2-related factor 2 (NRF2) to attenuate brain I/R injury in transcerebral I/R-injured rats and transoxygenic glucose deprivation/reperfusion (OGD/R)-injured SY5Y cells.
Material And Methods: Remimazolam was added at the beginning of cell and rat reperfusion, and the PI3K/AKT inhibitor LY294002 was added to inhibit the AKT/GSK-3β/NRF2 pathway 24 h before cellular OGD/R treatment and 30 min before rat brain I/R treatment.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!