Accumulating evidence suggests that glycogen synthase kinase 3 (GSK-3) is a multifunctional kinase implicated in Alzheimer's disease (AD). However, the synaptic actions of GSK-3 in AD conditions are largely unknown. In this study, we examined the impact of GSK-3 on N-methyl-D-aspartate receptor (NMDAR) channels, the major mediator of synaptic plasticity. Application of GSK-3 inhibitors or knock...

Testosterone induces cardiac hypertrophy through a mechanism that involves a concerted crosstalk between cytosolic and nuclear signaling pathways. Nuclear factor of activated T-cells (NFAT) is associated with the promotion of cardiac hypertrophy, glycogen synthase kinase-3β (GSK-3β) is considered to function as a negative regulator, mainly by modulating NFAT activity. However, the role played b...

Glycogen synthase kinase-3β (GSK-3β) plays an important role in the regulation of apoptosis. To investigate its involvement in acquired cadmium (Cd) resistance, Cd-resistant cells (RH460) were established from H460 lung carcinoma cells. Cd resistance led to interruption of apoptosis and autophagy, as determined by an apoptotic sub-G1 population, procaspase-3 clevage, and LC3-II induction. Cd-in...

Development of innovative more effective therapy is required for refractory osteosarcoma patients. We previously established that glycogen synthase kinase-3β (GSK- 3β) is a therapeutic target in various cancer types. In the present study, we explored the therapeutic efficacy of GSK-3β inhibition against osteosarcoma and the underlying molecular mechanisms in an orthotopic mouse model. Expressio...

Increased GSK-3 activity is believed to contribute to the etiology of chronic disorders like Alzheimer's disease (AD), schizophrenia, diabetes, and some types of cancer, thus supporting therapeutic potential of GSK-3 inhibitors. Numerous mouse models with modified GSK-3 have been generated in order to study the physiology of GSK-3, its implication in diverse pathologies and the potential effect...

BACKGROUND Glioma accounts for the majority of primary malignant brain tumors in adults. METHODS Glioma specimens and normal brain tissues were analyzed for the expression levels of GSK-3β and p-GSK-3β (Ser9) by tissue microarray analysis (TMA) and Western blotting. Glioma cells over-expressing GSK-3β were used to analyze biological functions both in vitro and in vivo. RESULTS The levels of...

Glycogen Synthase Kinase 3 (GSK-3) is a key player in development, physiology and disease. Because of this, GSK-3 inhibitors are increasingly being explored for a variety of applications. In addition most analyses focus on GSK-3β and overlook the closely related protein GSK-3α. Here, we describe novel GSK-3α and GSK-3β mouse alleles that allow us to visualise expression of their respective mRNA...

Letter by Karlstaedt and Taegtmeyer Regarding Article, “Loss of Adult Cardiac Myocyte GSK-3 Leads to Mitotic Catastrophe Resulting in Fatal Dilated Cardiomyopathy” To The Editor: We have read with interest the article by Zhou et al. The authors demonstrated that in cardiomyocytes, conditional deletion of glycogen synthase kinase-3 (GSK-3) isoforms A and B leads to development of severe dilated ...

Preconditioning (PreC) and postconditioning (PostC) have been shown to initiate a number of signaling cascades that reduce cell death. However, the mechanisms by which these signals reduce cell death have been elusive.1 PreC has been shown to phosphorylate and thereby inhibit glycogen synthase kinase (GSK)-3 , and perfusion with GSK inhibitors has been shown to reduce cell death induced by isch...

Glioblastoma is the most malignant form of brain cancer. Due to its aggressive nature, extensive research has been performed, but little progress has been made in identifying effective treatment options. Glycogen synthase kinase-3 (GSK-3) is a ubiquitous, multifaceted protein kinase. Previous studies have shown that small molecule inhibitors of GSK-3 block the migration of glioblastoma cells an...