CDKs and GSK3 as Kinase Screening Targets

We have focused our screening efforts on two families of kinases, the CDKs and GSK-3, as well as PfGSK-3, the GSK-3 homologue kinase in Plasmodium falciparum (the agent responsible for the lethal form of malaria) (Droucheau et al. 2004). CDKs are involved in controlling the cell cycle (CDK1, CDK2, CDK3, CDK4, CDK6, CDK7), apoptosis (CDK1, CDK2, CDK5), neuronal functions and neurodegeneration (CDK5, CDK11), transcription (CDK7, CDK8, CDK9) and exocytosis (review in Morgan 1997; Pavletich 1999; Malumbres et al. 2000; Dhavan and Tsai 2001; Harper and Adams 2001; Maccioni et al. 2001; Malumbres and Barbacid 2001; Knockaert et al. 2002a). GSK-3, an essential element of the Wnt signalling pathway, is involved in multiple physiological processes including cell cycle regulation by controlling the levels of cyclin D1 and b-catenin, dorso-ventral patterning during development, insulin action on glycogen synthesis, axonal outgrowth, HIV-1 Tat-mediated neurotoxicity, apoptosis, Alzheimer's disease characteristic phosphorylation of tau and amyloid-b production, and maintenance of "sternness" (review in Cohen and Frame 2001; Grimes and Jope 2001; Eldar-Finkelman 2002; Kaytor and Orr 2002; Doble and Woodgett 2003).

Potential applications of CDK/GSK-3 inhibitors are being evaluated for the treatment of cancers, neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and stroke, diabetes, restenosis, proliferation of protozoan parasites, and viral infections.

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Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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