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Title

GSK-3 Mouse Models to Study Neuronal Apoptosis and Neurodegeneration.

AuthorsGómez-Sintes, Raquel ; Hernández Pérez, Félix ; Lucas, José Javier ; Ávila, Jesús
KeywordsNeurodegenerative disorder
Alzheimer’s disease
GSK-3, apoptosis
Mouse models
Issue Date16-Nov-2011
CitationFrontiers in Molecular Neuroscience 4: 45 (2011)
AbstractIncreased GSK-3activityis believed to contribute to the etiology ofchronic disorders likeAlzheimer’sdisease(AD),schizophrenia,diabetes,andsometypesofcancer,thus supporting therapeutic potential ofGSK-3inhibitors.Numerous mouse models with modified GSK-3have been generated in order to study the physiology of GSK-3,its implication in diverse pathologies and the potential effect of GSK- 3inhibitors.In this review we have focused on the relevance of these mouse models for the study of the role of GSK-3 in apoptosis.GSK-3 s involved in two apoptotic pathways,intrinsic and extrinsic pathways,and plays opposite roles depending on the apoptotic signaling process that is activated.It promotes celldeath when acting through intrinsic pathway and plays an anti- apoptotic role if the extrinsi cpathway i soccurring. Itisimportant to dissect this duality since,among the diseases in which GSK-3is involved,excessive cell death is crucial in some illnesseslike neurodegenerative diseases,while a deficient apoptosis is occurring in others such as cancerorautoimmune diseases.Theclinical application of aclassicalGSK-3 inhibitor,lithium,is limited by its toxic consequences,including motorside effects.Recently,the mechanism leadingto activation of apoptosis following chronic lithium administration has been described.Understanding this mechanism could help tominimize side effects andto improve application of GSK-3inhibitors to the treatmentof AD and to extend the application to other diseases.
URIhttp://hdl.handle.net/10261/127754
Identifiersissn: 1662-5099
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