Search results for "GSK3B"
showing 4 items of 14 documents
Insulin resistance as common molecular denominator linking obesity to Alzheimer’s disease
2015
Alzheimer’s disease (AD) is an aging-related multi-factorial disorder to which metabolic factors contribute at what has canonically been considered a centrally mediated process. Although the exact underlying mechanisms are still unknown, obesity is recognized as a risk factor for AD and the condition of insulin resistance seems to be the link between the two pathologies. Using mice with high fat diet (HFD) obesity we dissected the molecular mechanisms shared by the two disorders. Brains of HFD fed mice showed elevated levels of APP and Aβ 40 /Aβ 42 together with BACE, GSK3β and Tau proteins involved in APP processing and Aβ accumulation. Immunofluorescence, Thioflavin T staining experiments…
Glycogen synthase kinase 3β links neuroprotection by 17β-estradiol to key Alzheimer processes
2004
Estrogen exerts many of its receptor-mediated neuroprotective functions through the activation of various intracellular signal transduction pathways including the mitogen activating protein kinase (MAPK), phospho inositol-3 kinase and protein kinase C pathways. Here we have used a hippocampal slice culture model of kainic acid-induced neurotoxic cell death to show that estrogen can protect against oxidative cell death. We have previously shown that MAPK and glycogen synthase kinase-3beta (GSK-3beta) are involved in the cell death/cell survival induced by kainic acid. In this model and other cellular and in vivo models we have shown that estrogen can also cause the phosphorylation and hence …
Expression profile of components of the β-catenin destruction complex in oral dysplasia and oral cancer
2021
Background Oral cancer represents the sixth most common cancer in the world and is associated with 40-50% survival at 5 years. Within oral malignancies, oral squamous cell carcinoma (OSCC) is commonly preceded by potentially malignant lesions, which, according to histopathological criteria, are referred to as oral dysplasia and their diagnosis are associated with higher rates of malignant transformation towards cancer. We recently reported that aberrant activation of the Wnt/β‑catenin pathway is due to overexpression of Wnt ligands in oral dysplasia. However, the expression of other regulators of this pathway, namely components of the β-catenin destruction complex has not been explored in o…
(±)- BIGI-3h: Pentatarget-Directed Ligand combining Cholinesterase, Monoamine Oxidase, and Glycogen Synthase Kinase 3β Inhibition with Calcium Channe…
2021
Multitarget-directed ligands (MTDLs) are considered a promising therapeutic strategy to address the multifactorial nature of Alzheimer's disease (AD). Novel MTDLs have been designed as inhibitors of human acetylcholinesterases/butyrylcholinesterases, monoamine oxidase A/B, and glycogen synthase kinase 3β and as calcium channel antagonists via the Biginelli multicomponent reaction. Among these MTDLs, (±)-BIGI-3h was identified as a promising new hit compound showing in vitro balanced activities toward the aforementioned recognized AD targets. Additional in vitro studies demonstrated antioxidant effects and brain penetration, along with the ability to inhibit the aggregation of both τ protein…