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[资源] Glycogen Synthase Kinase-3 (GSK-3) and Its Inhibitors

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