Thymosins

 
 
Academic Press
  • 1. Auflage
  • |
  • erschienen am 20. Juli 2016
  • |
  • 332 Seiten
 
E-Book | ePUB mit Adobe DRM | Systemvoraussetzungen
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978-0-12-805234-1 (ISBN)
 

Thymosins, the latest volume in the Vitamins and Hormones series, first published in 1943, and the longest-running serial published by Academic Press, provides up-to-date information on thymosins research that spans new data from molecular biology to the clinic.

Each volume can focus on a single molecule or a disease that is related to vitamins or hormones, with the topic broadly interprested to include related substances, such as transmitters, cytokines, growth factors, and others reviewed.


  • Provides cutting-edge reviews concerning the molecular and cellular biology of vitamins and hormones
  • Contains expertise from world-renowned contributors
  • Includes coverage of a vast array of subjects
  • Presents In-depth, current information at the molecular to the clinical levels
0083-6729
  • Englisch
  • San Diego
  • |
  • USA
Elsevier Science
  • 20,85 MB
978-0-12-805234-1 (9780128052341)
0128052341 (0128052341)
weitere Ausgaben werden ermittelt
  • Front Cover
  • Thymosins
  • Copyright
  • Former Editors
  • Contents
  • Contributors
  • Preface
  • Chapter One: Structures of Thymosin Proteins
  • 1. Introduction
  • 2. Structures of Prothymosin a and Parathymosin
  • 2.1. Native Structure of Prothymosin a
  • 2.2. pH-Induced Structures of Prothymosin a
  • 2.3. Structure of the Prothymosin a Carboxy-Terminal Peptide
  • 2.4. Structure of Prothymosin a in a Complex with the Keap1 Kelch Domain
  • 2.5. Structure of Prothymosin a in the Presence of Zn2+
  • 2.6. Structure of Parathymosin a
  • 3. Structures of Ta1
  • 3.1. Structure of Ta1 in Water
  • 3.2. Structure of Ta1 in Mixed Solvents
  • 3.3. Structure of Ta1 in Membrane-Like Environments
  • 4. Structures of Beta Thymosin Proteins
  • 4.1. Structure of Thymosin ß9
  • 4.2. Structure of Human Thymosin ß10
  • 4.3. Structure of Thymosin ß4
  • 4.4. Solution Phase Structure of Thymosin ß4 Interacting with Actin
  • 4.5. Crystallographic Structures of Thymosin ß4 Chimeras Interacting with Actin
  • 5. Conclusions
  • Acknowledgments
  • References
  • Chapter Two: Intrinsic, Functional, and Structural Properties of ß-Thymosins and ß-Thymosin/WH2 Domains in the Regulation ...
  • 1. Introduction
  • 2. The Sequences of ß-Thymosins and ß-Thymosin/WH2 Domains
  • 2.1. Isolated ß-Thymosins Expressed as Small Proteins of 5kDa
  • 2.2. ß-Thymosin Domains Expressed as Repeats and in Modular Proteins
  • 2.3. WH2 Domains in Multimodular Proteins
  • 2.4. General Features of the Sequences of ßT/WH2 Domains
  • 3. General Properties of Intrinsically Disordered Proteins/Domains
  • 3.1. Intrinsic and Protein-Protein Interaction Properties of IDPs/IDRs
  • 3.2. Main Functions of IDPs/IDRs
  • 4. Main Intracellular Function of ß-Thymosins and Functional Versatility of ßT/WH2 Domains in Actin Assembly
  • 4.1. ß-Thymosins as Genuine G-Actin Sequestering Proteins
  • 4.2. Extension of the Functions of ßT/WH2 Domains in Actin Assembly
  • 4.2.1. Functional Versatility of ßT and WH2 as Individual Domains
  • 4.2.2. Functional Versatility as Repeats or in Association with Other Domains/Proteins
  • 5. Individual WH2/ßT IDRs and G-Actin Form Fuzzy Complexes to Regulate Either Sequestering or Profilin-Like Functions in A ...
  • 6. Conclusions
  • References
  • Chapter Three: Actin-Induced Structure in the Beta-Thymosin Family of Intrinsically Disordered Proteins
  • 1. Introduction
  • 2. Beta-Thymosins in Solution
  • 2.1. Tß4 in Mixed Organic-Aqueous Solvent
  • 2.2. Tß4 in Aqueous Solution
  • 2.3. Tß10 in Mixed Organic-Aqueous Solvent
  • 2.4. Tß4 Mutants in Mixed Organic-Aqueous Solvent
  • 3. Beta-Thymosins in Complex with Actin
  • 3.1. NMR-Based Tß4:Actin Model
  • 3.2. X-ray Structures
  • 3.2.1. C-Terminal Segment of Tß4
  • 3.2.2. N-Terminal Segment of Ciboulot´s First ßT Repeat
  • 3.2.3. C-Terminal Segment of Ciboulot´s Second ßT Repeat
  • 3.2.4. Structure-Based Models of Tß4
  • 3.2.5. Full-Length and N-Terminal Segment of Tß4
  • 4. Tß4:Actin Interface Analysis
  • 5. Conclusion
  • Acknowledgments
  • References
  • Chapter Four: Phosphorylation of Prothymosin a. An Approach to Its Biological Significance
  • 1. Introduction
  • 1.1. The Precursor of the a-Thymosins
  • 1.2. Progress in the Study of the Biological Function of ProTa
  • 2. Phosphorylation In vitro vs In vivo
  • 3. The Protein Kinase Which Phosphorylates ProTa in Proliferating Cells
  • 3.1. Characterization of the Purified ProTa Kinases
  • 3.2. Characterization of the Cytoplasmic Kinase that Phosphorylates ProTa
  • 4. About the Biological Significance of the Phosphorylation of ProTa
  • 5. Concluding Remarks and Perspectives
  • References
  • Chapter Five: Mechanism of Action of Thymosina1: Does It Interact with Membrane by Recognition of Exposed Phosphatidylseri ...
  • 1. Introduction
  • 2. The NMR Structural Study in Trifluoroethanol Solution
  • 3. The Structural Study by NMR in Micellar Environment
  • 4. The Interactions with Phospholipidic Membranes with Negative Regions
  • 5. The Conformation of Thymosina1 in Mixed DPC-d38/SDS-d25 Micelles
  • 6. The Interaction of Thymosina1 with Perdeuterated DPC and Perdeuterated DPC-SDS Micelles
  • 7. The Circular Dichroism Study of Thymosina1 in Perdeuterated DPC and Perdeuterated DPC-SDS Micelles
  • 8. The Structural Study by NMR of the Interaction of Thymosina1 with Phosphatidylserine in Membranes
  • 9. 15N NMR Spectroscopy Study of the Interaction
  • 10. Implications of Thymosina1 Binding to PS Exposure
  • 11. Implication of Thymosina1 Binding to Membrane and Cells
  • Acknowledgments
  • References
  • Chapter Six: Thymosin Beta 4 Is a Potential Regulator of Hepatic Stellate Cells
  • 1. Introduction
  • 2. Liver Cells and Diseases
  • 3. Hepatic Stellate Cells
  • 4. Thymosin Beta 4
  • 5. Tß4 in Liver
  • 5.1. Hepatic Expression of Tß4
  • 5.2. The Potential Role of Exogenous Tß4 in Liver
  • 5.3. The Potential Role of Endogenous Tß4
  • 5.4. The Effects of the Ac-SDKP Fragment of Tß4 in Liver Disease
  • 5.5. The Tß4 Signaling Pathway in the Liver
  • 5.6. Tß4 in Liver Cancers
  • 6. Conclusions and Future Directions
  • Acknowledgments
  • References
  • Chapter Seven: Immune Modulation with Thymosin Alpha 1 Treatment
  • 1. Introduction
  • 2. Mechanism of Immune Reconstitution with Ta1
  • 3. Preclinical Studies of Ta1 in Immune Suppressed Animals
  • 3.1. Animal Models of Infectious Disease
  • 3.2. Animal Models of Cancer
  • 3.3. Animal Models of Improvement in Vaccine Response
  • 4. Clinical Studies of Ta1 in Immune Suppression
  • 4.1. Clinical Studies in Primary Immune Deficiency
  • 4.2. Clinical Studies in Infectious Disease
  • 4.2.1. Acute Infections
  • 4.2.2. Chronic Infections
  • 4.3. Clinical Studies in Cancer
  • 4.3.1. Melanoma
  • 4.3.2. Hepatocellular Carcinoma
  • 4.3.3. Non-Small Cell Lung Cancer
  • 4.3.4. Quality of Life in Cancer
  • 4.4. Clinical Studies in Vaccine Enhancement
  • 5. Conclusions and Future Directions
  • Acknowledgments
  • References
  • Chapter Eight: Prothymosin Alpha and Immune Responses: Are We Close to Potential Clinical Applications?
  • 1. Introduction
  • 2. Historical Overview on ProTa Isolation and Properties
  • 2.1. Thymosin Fraction V: The First Immunoactive Thymic Extract
  • 2.2. Dissecting TFV: Isolation of the First Immunoactive Thymosins
  • 2.3. ProTa: Major Structural Characteristics and Properties
  • 3. The Multifaceted Immune Activities of ProTa
  • 3.1. The Thoroughly Studied Anticancer Activity of ProTa
  • 3.2. Antiviral Activities of ProTa
  • 3.3. ProTa Exerts Neuroprotective Functions
  • 3.4. Miscellaneous Functions Reported for ProTa
  • 4. The Immunostimulatory Activity of ProTa-Derived Peptides
  • 4.1. The Amino-Terminal Peptide Ta1 Has Shown Some Immune Activity
  • 4.2. The Carboxy-Terminal ProTa Peptides Exhibit Improved Immune Functions
  • 4.3. The Immune Activity of ProTa Middle Segment Peptides
  • 5. Evidence Supporting a Dual-Intracellular and Extracellular-Role for ProTa
  • 5.1. The Intracellular Role of ProTa
  • 5.2. The Extracellular Role of ProTa
  • 5.3. Evidence Suggesting That ProTa May Act as an Alarmin
  • 6. Proposed Scenario for the Mechanism of Action of ProTa
  • 7. Conclusions and Future Directions
  • Acknowledgments
  • References
  • Chapter Nine: Cardioprotection by Thymosin Beta 4
  • 1. Introduction
  • 2. Basic Properties of Tß4: Expression, Structure, and Interaction with Actin
  • 3. Signaling Pathways Downstream of Tß4
  • 3.1. Actin-Dependent
  • 3.2. Actin-Independent
  • 3.3. Extracellular Receptor-Mediated
  • 4. Cell and Tissue Effects Relevant to Cardioprotection
  • 5. Cardioprotection in Preclinical Animal Models
  • 6. Clinical Studies
  • 7. Conclusions
  • References
  • Chapter Ten: Thymosin ß4: Roles in Development, Repair, and Engineering of the Cardiovascular System
  • 1. Introduction
  • 2. Development of the Cardiac System
  • 2.1. General Timeline
  • 2.2. Role of Thymosin ß4 in Fetal Development
  • 3. Progression and Repair After Disease
  • 3.1. Pathogenesis of Heart Attack
  • 3.2. Pathogenesis of Stroke and Subsequent Repair
  • 4. Tissue Engineering Using Tß4
  • 4.1. Direct Injections
  • 4.2. Tß4 as a Scaffold Coating
  • 4.3. Tß4 and Cell Differentiation
  • 5. Conclusion and Future Directions
  • References
  • Chapter Eleven: Thymosin ß4 Promotes Dermal Healing
  • 1. Introduction
  • 2. Human Dermal Healing
  • 3. Stages in Dermal Healing
  • 3.1. Inflammation
  • 3.2. Proliferation
  • 3.3. Remodeling
  • 4. Tß4 Activity
  • 4.1. Activity in Wounds
  • 4.2. Tß4 Activity in Dermal Burns
  • 4.3. Active Sites in Tß4 and Cell Surface Receptor
  • 4.3.1. Peptide 1-4
  • 4.3.2. Peptide 1-15
  • 4.3.3. Peptide 17-23
  • 4.3.4. Peptide 40-43 (AGES)
  • 4.3.5. Other Activities in Unknown Sequences
  • 4.3.6. Cell Surface Receptor ATP Synthase
  • 4.4. Tß4 Does Not Promote Cell Growth
  • 5. Preclinical Animal Studies with Tß4
  • 6. Human Dermal Studies with Tß4
  • 6.1. Phase 1 Topical Safety Trial
  • 6.2. Phase 2 Trials on Patients with Pressure Ulcers, Stasis Ulcers, and Epidermolysis Bullosa Lesions
  • 6.2.1. Pressure Ulcers (NCT00382174)
  • 6.2.2. Venous Stasis Ulcers (NCT00832091)
  • 6.2.3. Epidermolysis Bullosa Wounds (NCT00311766)
  • 7. Thymosin ß4 Safety
  • 8. Conclusions and Future Studies with Tß4 in Dermal Wound Repair
  • 8.1. What We Know
  • 8.2. What We Do Not Know
  • References
  • Chapter Twelve: Thymosin Beta 4: A Potential Novel Therapy for Neurotrophic Keratopathy, Dry Eye, and Ocular Surface Diseases
  • 1. Introduction
  • 2. Tß4 in Wound Healing
  • 3. Tß4 and Inflammation
  • 4. Neurotrophic Keratopathy
  • 5. Treatment for NK
  • 6. Wound Healing and Antiinflammatory Effects of Tß4
  • 7. Clinical Efficacy of Tß4 in Wound Healing Due to NK
  • 8. Dry Eye Disease
  • 9. Efficacy of Tß4 in Animal Models of Dry Eye
  • 10. Clinical Efficacy of Tß4 in Dry Eye
  • 11. Clinical Safety Evaluations of Tß4
  • 12. Potential Indications for Tß4
  • 13. Conclusion
  • References
  • Index
  • Color Plate
  • Back Cover

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