[GSK-3beta: a central kinase for neurodegenerative diseases?].
Neurodegenerative diseases are more and more prevalent in our aging societies. There is strong evidence that glycogen synthase kinase (GSK)-3b plays a crucial role in Alzheimer's disease (AD). Indeed, it is involved in the regulation of the two major neuropathological hallmarks present in the brains of AD patients. Interestingly, the kinase has been implicated in multiple cellular processes and linked with the pathogenesis and neuronal loss in several neurodegenerative diseases, including Parkinson's and Huntington's diseases, in which abnormally elevated levels of GSK-3b activity have been reported. In this review, we will provide an overview of the current data pointing out the convergent role of GSK-3b in the neuropathological pathways of these diseases. We will also discuss the rationale for the development of specific inhibitors with therapeutic potentials for such devastating human diseases.
Petit-Paitel
Agnès
A
Institut de pharmacologie moléculaire et cellulaire, route des Lucioles, Sophia Antipolis, Valbonne, France. petit@ipmc.cnrs.fr
D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002352:Carrier Proteins / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D016631:Lewy Bodies; D008928:Mitochondria / Q000502:physiology; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000517:prevention & control; D016874:Neurofibrillary Tangles / Q000201:enzymology; D010300:Parkinson Disease / Q000201:enzymology; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000201:enzymology; D053763:Presenilins / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011499:Protein Processing, Post-Translational; D051844:alpha-Synuclein / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D053763:Presenilins; D047428:Protein Kinase Inhibitors; C118958:SNCAIP protein, human; D051844:alpha-Synuclein; D016875:tau Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3