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Glycogen Synthase Kinase-3 (GSK-3) and Its Inhibitors
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Glycogen Synthase Kinase-3 (GSK-3) and Its Inhibitors: Drug Discovery and Development Ana Martinez, Ana Castro, Wiley 2006 ISBN-10: 0471770019 Glycogen Synthase Kinase 3 (GSK–3) was discovered about twenty–five years ago but had garnered little interest until recently. Now many researchers believe that there is much potential for this "old" enzyme and are re–examining its biological characteristics. GSK–3 and its inhibitors could lead to effective treatments for neurogenerative disorders, type II diabetes, depression and bipolar disorder, and some forms of cancer. This book explores the nature of this promising enzyme, providing a thorough introduction and discussion, and mentions the birth of several chemical families of GSK–3 inhibitors with varying selectivity. CONTENTS FOREWORD—THE ORIGINS OF GSK-3 ix PREFACE xvii ACKNOWLEDGMENTS xix CONTRIBUTORS xxi ABBREVIATIONS xxv PART I CELLULAR FUNCTIONS OF GSK-3 1 1 Glycogen Synthase Kinase 3: An Introductory Synopsis 3 2 Glycogen Synthase Kinase 3b (GSK-3b) a Key Signaling Enzyme: A Developmental Neurobiological Perspective 25 3 Role of GSK-3/Shaggy in Neuronal Cell Biology 45 4 The Crystal Structures of Glycogen Synthase Kinase 3 61 5 Kinase–Kinase and Site–Site Interactions in the Phosphorylation of Tau by GSK-3 83 PART II GSK-3 AS A THERAPEUTIC TARGET IN HUMAN PATHOLOGY 105 6 GSK-3, a Key Player in Alzheimer’s Disease 107 7 Glycogen Synthase Kinase 3: A Target for Novel Mood Disorder Treatments 125 8 GSK-3 and Stem Cells 155 9 Glycogen Synthase Kinase 3: Role in Neurodegeneration and Neuroprotection 173 10 Protein Kinase Assays for Drug Discovery 189 11 Animal Models with Modifi ed Expression of GSK-3 for the Study of Its Physiology and of Its Implications in Human Pathologies 203 PART III GSK-3 INHIBITORS: DEVELOPMENT AND THERAPEUTIC POTENTIAL 221 12 Lithium, the Seminal GSK-3 Inhibitor 223 13 Inhibition of GSK-3 as Therapeutic Strategy in Disease: Effi cacy of AR-A014418 243 14 TDZD’s: Selective and ATP Noncompetitive Glycogen Synthase Kinase 3 Inhibitors 257 15 3-Amino Pyrazoles as Potent and Selective Glycogen Kinase Synthase 3 (GSK-3) Inhibitors 281 16 Marine Compounds as a New Source for Glycogen Synthase Kinase 3 Inhibitors 307 INDEX 333  |
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2016-07-17 18:05:00, 7.89 M
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