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Glycogen Synthase Kinase-3 International Journal of Alzheimer’s Disease Glycogen Synthase Kinase-3 Guest Editors: Peter Crouch, Adam Cole, Michael Cousin, Ana Martinez, and Katja Kanninen Glycogen Synthase Kinase-3 International Journal of Alzheimer’s Disease Glycogen Synthase Kinase-3 Guest Editors: Peter Crouch, Adam Cole, Michael Cousin, Ana Martinez, and Katja Kanninen Copyright © 2011 SAGE-Hindawi Access to Research. All rights reserved. This is a special issue published in volume 2011 of “International Journal of Alzheimer’s Disease.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board D. Allsop, UK George Grossberg, USA Michal Novak,´ Slovakia Craig S. Atwood, USA Harald J. Hampel, Germany Leonardo Pantoni, Italy Brian Austen, UK K. Jellinger, Austria Francesco Panza, Italy Jesus Avila, Spain Mark S. Kindy, USA Lucilla Parnetti, Italy B. J. Bacskai, USA Amos D. Korczyn, Israel George Perry, USA Andrew Budson, USA Jeff Kuret, USA M. Cristina Polidori, Germany Roger A. Bullock, UK Andrew J. Larner, UK John Powell, UK A. I. Bush, USA Hyoung-gon Lee, USA Jeffrey R. Powell, USA Gemma Casadesus, USA Jerzy Leszek, Poland Marcella Reale, Italy Rudolph J. Castellani, USA Seth Love, UK Vincenzo Solfrizzi, Italy James R. Connor, USA Michelangelo Mancuso, Italy Akihiko Takashima, Japan Suzanne M. de la Monte, USA James G. McLarnon, Canada Matti Viitanen, Sweden Justo G. de Yebenes, Spain P. Me co cc i, Ita ly Bengt Winblad, Sweden Sara M. Debanne, USA Kenichi Meguro, Japan David Yew, Hong Kong Steven D. Edland, USA Judith Miklossy, Canada Henrik Zetterberg, Sweden Cheng-Xin Gong, USA PaulaI.Moreira,Portugal Paula Grammas, USA Ricardo Nitrini, Brazil Contents Glycogen Synthase Kinase-3, Peter Crouch, Adam Cole, Michael Cousin, Ana Martinez, and Katja Kanninen Volume 2011, Article ID 279234, 1 page Deconstructing GSK-3: The Fine Regulation of Its Activity, Miguel Medina and Francisco Wandosell Volume 2011, Article ID 479249, 12 pages What Are the bona fide GSK3 Substrates?, Calum Sutherland Volume 2011, Article ID 505607, 23 pages The Role of GSK3 in Presynaptic Function, Karen Janet Smillie and Michael Alan Cousin Volume 2011, Article ID 263673, 8 pages GSK3 Function in the Brain during Development, Neuronal Plasticity, and Neurodegeneration, Pamela Salcedo-Tello, Abril Ortiz-Matamoros, and Clorinda Arias Volume 2011, Article ID 189728, 12 pages GSK-3 in Neurodegenerative Diseases, Peng Lei, Scott Ayton, Ashley I. Bush, and Paul A. Adlard Volume 2011, Article ID 189246, 9 pages Regulation of Cell Survival Mechanisms in Alzheimer’s Disease by Glycogen Synthase Kinase-3, Marjelo A. Mines, Eleonore Beurel, and Richard S. Jope Volume 2011, Article ID 861072, 11 pages Glycogen Synthase Kinase-3β: A Mediator of Inflammation in Alzheimer’s Disease?, Jari Koistinaho, Tarja Malm, and Gundars Goldsteins Volume 2011, Article ID 129753, 9 pages Functional Implications of Glycogen Synthase Kinase-3-Mediated Tau Phosphorylation, Diane P. Hanger and Wendy Noble Volume 2011, Article ID 352805, 11 pages Targeting Glycogen Synthase Kinase-3β for Therapeutic Benefit against Oxidative Stress in Alzheimer’s Disease: Involvement of the Nrf2-ARE Pathway, Katja Kanninen, Anthony R. White, Jari Koistinaho, and Tarja Malm Volume 2011, Article ID 985085, 9 pages Glycogen Synthase Kinase 3 Inhibitors in the Next Horizon for Alzheimer’s Disease Treatment, Ana Martinez, Carmen Gil, and Daniel I. Perez Volume 2011, Article ID 280502, 7 pages SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 279234, 1 page doi:10.4061/2011/279234 Editorial Glycogen Synthase Kinase-3 Peter Crouch,1 Adam Cole,2 Michael Cousin,3 Ana Martinez,4 and Katja Kanninen5 1 Department of Pathology and Centre for Neuroscience, The University of Melbourne and Mental Health Research Institute, Parkville, VIC 3010, Australia 2 Neurosignalling Group, Garvan Institute for Medical Research, 384 Victoria St. Darlinghurst, Sydney, NSW 2010, Australia 3 Membrane Biology Group, Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh EH8 9XD, UK 4 Instituto Quimica Medica (C.S.I.C.), Juan de la Cierva 3, 28006 Madrid, Spain 5 Department of Neurobiology, A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland Correspondence should be addressed to Peter Crouch, [email protected] Received 2 November 2011; Accepted 2 November 2011 Copyright © 2011 Peter Crouch et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Glycogen synthase kinase-3 (GSK3) is a ubiquitous and pro- and M. A. Cousin) and the second on GSK3 in brain miscuous kinase that has been studied extensively for over development and neuronal plasticity (P. Salcedo-Tello et al.). four decades. Initial reports beginning in the 1970s described After this the contribution of GSK3 to neurodegenerative its role in cellular metabolic pathways fundamental to glu- diseases is described in four reviews. The first describes cose metabolism, but in more recent years the number of GSK3 in neurodegenerative diseases in general (P. Lei et al.) reports describing aberrant GSK3 activity in pathological while the following three discuss more specific aspects of conditions has risen dramatically. Alzheimer’s disease, including cell survival mechanisms (M. Interest in GSK3 in the field of Alzheimer’s disease was A. Mines et al.), inflammation (j. Koistinaho et al.), and first sparked in the early 1990s by papers that described tau phosphorylation (D. P. Hanger and W. Nobel). Finally, the ability of GSK3 to phosphorylate tau. Excessive tau the special issue concludes with two reviews on therapeutic phosphorylation is present in Alzheimer’s-disease-affected strategies for Alzheimer’s disease that focus on GSK3. The brain. These early papers provided new insight to the mech- potential of targeting GSK3 for therapeutic benefit against anisms that may contribute to tau pathology of Alzheimer’s, oxidative stress is presented (K. Kanninen et al.), followed with GSK3 as a potential central figure. Since then, the by an appraisal of GSK3 inhibitors in the next horizon (A. research effort invested into GSK3 in Alzheimer’s disease Martinez et al.). has expanded, and mechanistic studies now demonstrate a Since several GSK3 inhibitors are currently in clinical functional relationship between not only GSK3 and tau, trials for treatment of neurological and other disorders, we but also GSK3 and amyloid-β. Through weight of numbers, feel this special issue is a timely “snapshot” of our current strong evidence now indicates that GSK3 is associated with knowledge of GSK3 function in healthy and diseased brain, the two key pathological features of Alzheimer’s-disease- and highlights outstanding issues for future research on this affected brain: neurofibrillary tangles and amyloid plaques. important brain kinase. The scope of this special issue is to provide an overview Peter Crouch of the data that implicate GSK3 in Alzheimer’s disease. As Adam Cole an introduction, the special issue begins with a review of the Michael Cousin regulation of GSK3 activity (M. Medina and F. Wandosell). Ana Martinez This is followed by a report that provides caution by ar- Katja Kanninen ticulating the need to demonstrate the bona fide substrates of GSK3 (C. Sutherland). The role of GSK3 in the brain and neuronal function is then introduced by two reports. The first is on presynaptic function of GSK3 (K. J. Smillie SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 479249, 12 pages doi:10.4061/2011/479249 Review Article Deconstructing GSK-3: The Fine Regulation of Its Activity Miguel Medina1 and Francisco Wandosell2 1 NOSCIRA S.A., Tres Cantos, 28760 Madrid, Spain 2 Centro de Biolog´ıa Molecular “Severo Ochoa,” CSIC-UAM-CIBERNED Nicol´as Cabrera 1, 28049 Madrid, Spain Correspondence should be addressed to Francisco Wandosell, [email protected] Received 21 February 2011; Accepted 28 February 2011 Academic Editor: Peter Crouch Copyright © 2011 M. Medina and F. Wandosell. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Glycogen synthase kinase-3 (GSK-3) unique position in modulating the function of a diverse series of proteins in combination with its association with a wide variety of human disorders has attracted significant attention to the protein both as a therapeutic target and as a means to understand the molecular basis of these disorders. GSK-3 is ubiquitously expressed and, unusually, constitutively active in resting, unstimulated cells. In mammals, GSK-3α and β are each expressed widely at both the RNA and protein levels although some tissues show preferential levels of some of the two proteins. Neither gene appears to be acutely regulated at the transcriptional level, whereas the proteins are controlled posttranslationally, largely through protein-protein interactions or by posttranslational regulation. Control of GSK-3 activity thus occurs by complex mechanisms that are each dependent upon specific signalling pathways. Furthermore, GSK-3 appears to be
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