Activation of GSK-3beta is presumed to be involved in various neurodegenerative diseases, including Alzheimer's disease (AD), which is characterized by memory disturbances during early stages of the disease. The normal function of GSK-3beta in adult brain is not well understood. Here, we analyzed the ability of heterozygote GSK-3beta knockout (GSK+/-) mice to form memories. In the Morris water ...

The title compound (S)-3-(3-((7-ethynyl-9H-pyrimido[4,5-b]indol-4-yl)amino)piperidin-1-yl)propanenitrile (2) was synthesized in five steps, starting from 4-chloro-7-iodo-9H-pyrimido[4,5-b]indole (3), and characterized by 1H-NMR, 13C-NMR, MS HPLC. Moreover, its structure confirmed single crystal X-ray diffraction. Pyrimido[4,5-b]indole 2 demonstrated an IC50 value of 2.24 µM a NanoBRETTM TE intr...

Glycogen synthase kinase 3 (GSK-3) is implicated in neuronal death through a causal role, and precise mechanisms have not been unambiguously defined. We show that short hairpin RNA (shRNA) knockdown of GSK-3beta, but not GSK-3alpha, protects cerebellar granule neurons from trophic-deprivation-induced death. Using compartment-targeted inhibitors of the Wnt-regulated GSK-3 pool, NLS-FRAT1, NES-FR...

Insulin signaling pathways potentially involved in regulation of skeletal muscle glycogen synthase were compared in differentiated human muscle cell cultures from nondiabetic and type 2 diabetic patients. Insulin stimulation of glycogen synthase activity as well as phosphorylation of MAPK, p70 S6 kinase, and protein kinase B (Akt) were blocked by the phosphatidylinositol 3-kinase inhibitors wor...

Reactive oxygen species (ROS) at high concentrations induce oxidative stress, an imbalanced redox state that is a prevalent cause of neurodegenerative disorders. This study aimed to investigate the protective effect Capsosiphon fulvescens (CF) extract on stress-induced impairment cognitive function in models diseases. CF was extracted with subcritical water and several solvents H2O2 (0.25 mM) o...

Extracts of rat tissues contain kinases which catalyze the conversion of glycogen synthase from the glucose 6-phosphate-independent (I) form to the glucose 6-phosphate-dependent (D) form. These kinases were stimulated by adenosine 3’:5’ monophosphate (cyclic AMP). The glycogen synthase kinase activity ratio (activity in the absence of cyclic AMP divided by activity in the presence of cyclic AMP...