Glycogen Synthase Kinase 3 (GSK-3) and Its Inhibitors

Many researchers believe that 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 provides a thorough introduction to GSK-3, presents up-to-date information, and mentions the birth of several chemical families of GSK-3 inhibitors with varying selectivity. It’s a great reference for researchers in drug design and development. Foreword: The Origins of GSK-3.

Preface.

Acknowledgments.

Contributors.

Abbreviations.

PART I: CELLULAR FUNCTIONS OF GSK-3.

1. Glycogen Synthase Kinase-3 - an Introductory Synopsis .

2. Glycogen-Synthase-Kinase-β (GSK-3β) a Key Signaling Enzyme: A Developmental Neurobiological Perspective.

3. Role of GSK3/Shaggy in neuronal cell biology.

4. The Crystal Structures of Glycogen Synthase Kinase 3.

5. Kinase-Kinase and Site-Site Interactions in the Phosphorylation of Tau by GSK-3.

PART II: GSK3 AS A THERAPEUTIC TARGET IN HUMAN PATHOLOGY.

6. GSK-3, a Key Player in Alzheimer’s Disease.

7. Glycogen Synthase Kinase-3: A Target for Novel Mood Disorder Treatments.

8. GSK3 and Stem Cells.

9. Glycogen Synthase Kinase-3: role in Neurodegeneration and Neuroprotection.

10. Protein Kinase Inhibitors. Assay Development.

11. Animal Models with Modified Expression of GSK-3 for the Study of Its Physiology and of Its Implications in Human Pathologies.

PART III: GSK-3 INHIBITORS: DEVELOPMENT AND THERAPEUTIC POTENTIAL.

12. Lithium, the Seminal GSK3 Inhibitor.

13. Inhibition of GSK3 as Therapeutic Strategy in Disease: Efficacy of AR-A014418.

14. TDZD’s: Selective And ATP Non Competitive Glycogen Synthase Kinase-3 Inhibitors.

15. 3-Amino Pyrazoles as Potent and Selective Glycogen Synthase (GSK-3) Inhibitors.

16. Marine compounds as a new source for Glycogen Synthase Kinase-3 Inhibitors.

Index. ANA MARTINEZ is the Research and Development Director for NeuroPharma. She has been and still is an active researcher in the design and synthesis of GSK-3 inhibitors.

ANA CASTRO is the Medicinal Chemistry Director of NeuroPharma. She was formerly a tenured scientist at the Medicinal Chemistry Institute.

MIGUEL MEDINA is the Drug Discovery Director at NeuroPharma. He was formerly an instructor at the Brigham and Women's Hospital and the Harvard Medical School.

The new potential of an "old" enzyme

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.

Specific topics relating to GSK-3 covered in this book include:

• Cellular functions
• Neuronal cell biology
• Crystal structures
• Kinase-kinase and site-site interactions in the phosphorylation of tau
• Therapeutic target in human pathology
• Role in stem cells
• Physiology studies
• Development and therapeutic potential of GSK-3 inhibitors

Gathering and systematically analyzing relevant and up-to-date information about GSK-3 and its known inhibitors, this book will aid researchers interested in drug design and development, especially those directly involved in the fascinating world of GSK-3.