BOOKS BY CATEGORY
Your Account
Neurotrophic Factors
Price
Quantity
€139.08
(To see other currencies, click on price)
Paperback / softback
Add to basket  

MORE ABOUT THIS BOOK

Main description:

The pharmacology of neurotrophic factors is part of the general field called neuroprotection or neurodegeneration, which has emerged during the past two decades. This new broad research area has identified molecular mechanisms that regulate the morphological plasticity of the nervous system and, in con sequence, discovered novel pharmacological approaches to manipulate these processes in disease states. The new, structural neuropharmacology as de scribed in this volume attempts to regulate the anatomic aspects of the nervous system and is perhaps comparable to hardware manipulation in computer systems. In contrast, classical neuropharmacology identified multiple ways to modify the function of existing synapses or ion channels in the nervous system, comparable to software manipulations in the computer field. The pharmacol ogy of neurotrophic factor is at an early stage and has not produced any major drugs yet. However, the first quintessential clinical trials have been carried out in the past two years or are currently in progress. Rapid further advances can be expected. The discovery of nerve growth factor (NGF), the first protein known to promote survival and growth of nerve cells, led to the discovery of a family of related proteins, the neurotrophins and their receptors. This concept was generalized to incorporate many other protein families that are included in the functional definition of neurotrophic factors, i. e. , proteins able to regulate survival and differentiation of neurons.


Contents:

1 Biological Roles of Neurotrophins.- A. Introduction.- B. Neurotrophins in Different Species.- C. Trophic Roles of Neurotrophins in the Peripheral Nervous System.- I. Sensory Neurons.- 1. Nerve Growth Factor.- 2. Brain-Derived Neurotrophic Factor.- 3. Neurotrophin-3.- 4. Neurotrophin-4/5.- II. Sympathetic Neurons.- D. Trophic Roles of Neurotrophins in the Central Nervous System.- I. Prevention of Cell Death.- II. Other Trophic Actions.- 1. Regulation of Gene Expression.- 2. Functional and Morphological Effects on the Developing Cortex and Motoneurons.- E. Synaptic Transmission.- F. Modulation of Transcription of Neurotrophin Genes.- G. Regressive Events and Neurotrophins.- H. Conclusions and Perspectives.- References.- 2 Molecular Anatomy of Neurotrophic Factors.- A. Multi-Component Receptors, Specificity and Cross-Talk.- B. Insights into Neurotrophic-Factor Function from Structural Analyses.- C. Electrostatic Forces and the Interaction of Neurotrophic Factors with Their Receptors.- D. Site-Directed Mutagenesis and Structure-Activity Relationships.- E. Ligands with Altered Receptor-Binding Specificity Offer New Insights into Neurotrophic Factor Function.- F. Conclusions.- References.- 3 Neurotrophin Treatment of Peripheral Sensory Neuropathies.- Abbreviations.- A. Introduction.- B. Organization of the Peripheral Nervous System.- I. Sensory Neurons.- II. Sympathetic Neurons.- III. Parasympathetic Neurons.- C. Role of NGF in PNS Development.- D. Role of NGF in the Adult PNS.- E. NGF Receptors.- I. Expression in Normal Nerves.- II. Expression in Injured Nerves.- III. Alterations in NGF and NGF-Receptor Expression in Human Diabetic Neuropathy.- F. The Role of Neurotrophins in the Pathogenesis of Peripheral Sensory Neuropathies.- I. Pharmacology of Neurotrophins in Chemotherapeutic-Induced (Toxic) Peripheral Sensory Neuropathies.- II. Pharmacology of NGF in Experimental Diabetic Neuropathy.- 1. Therapeutic Effects of NGF in Experimental Diabetic Neuropathy.- III. Summary.- G. Clinical Peripheral Sensory Neuropathies: Diabetic Polyneuropathy.- I. Epidemiology of Diabetic Neuropathy.- II. Current Treatment of Peripheral Sensory Neuropathies.- H. Trial Design Considerations for the Study of Peripheral Sensory Neuropathies.- I. Selection of Study Endpoints.- II. Study Endpoints for Evaluation of Efficacy of rhNGF.- I. Clinical Studies of Nerve Growth Factor.- I. Safety, Pharmacokinetics and Pharmacodynamic Effects of rhNGF.- II. Preliminary Evidence of Efficacy of rhNGF in the Treatment of Peripheral Sensory Neuropathies.- J. Interpretation of Clinical-Trial Results.- K. Conclusions.- References.- 4 Neurotrophic Factors and Amyotrophic Lateral Sclerosis.- A. Introduction.- I. Developmental Cell Death of Motoneurons.- II. Pathological Cell Death of Motoneurons and Human Motoneuron Disease.- III. Why Should Neurotrophic Factors Interfere with the Pathogenic Mechanisms in Sporadic ALS?.- IV. Ciliary Neurotrophic Factor (CNTF) and Related Molecules.- 1. The CNTF Receptor Complex: Actions of Leukemia Inhibitory Factor, Oncostatin M and Cardiotrophin-1 Are Mediated Through Shared Receptor Subunits.- 2. The Function of Endogenous CNTF and Related Factors for Motoneurons.- 3. Pharmacological Effects of CNTF on Lesioned Motoneurons.- 4. Effects of CNTF and Other Neurotrophic Factors in Murine Animal Models for Motoneuron Disease.- 5. Pharmacological Effects of Systemically Applied CNTF.- V. The Effects of Neurotrophins on Motoneurons.- 1. Nerve Growth Factor.- 2. The Effects of Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3) and Neurotrophin-4/5 (NT-4/5) on Motoneurons.- 3. Physiological Functions of Neurotrophins for Motoneurons, As Revealed by Gene Targeting.- 4. Pharmacological Potential of Neurotrophins for Treatment of Amyotrophic Lateral Sclerosis.- VI. Glial-Derived Neurotrophic Factor.- 1. Specificity of GDNF for Motoneurons and Neuronal Populations in the Peripheral Nervous System.- 2. Physiological Function of GDNF: Evidence from Gene Knockout Studies.- 3. The Pharmacological Potential of GDNF for Treatment of Human Motoneuron Disease.- VII. Insulin-Like Growth Factors (IGF).- 1. Specific Function of IGF-I on Developing and Postnatal Motoneurons.- 2. Pharmacokinetics of IGF-I.- 3. Effects of IGF-I in Animal Models of Motoneuron Degeneration.- VIII. Future Perspectives: Are Newest Clinical Trials in ALS Patients with Neurotrophic Factors Meaningful?.- 1. Strategies to Increase the Availability of Pharmacologically Applied Neurotrophic Factors to Degenerating Motoneurons.- 2. Development of Modified Factors with Increased Specificity and Improved Pharmacokinetic Properties.- 3. Combinations of Neurotrophic Factors: The Better Strategy?.- References.- 5 Neuropharmacology of Insulin-Like Growth Factors.- Abbreviations.- A. Introduction.- B. Background.- I. IGF Genes and Transcripts.- 1. IGF-I.- 2. IGF-II.- II. IGF Receptors.- 1. Type-I Receptors.- 2. Type-II Receptors.- III. IGF Binding Proteins.- C. Neurotrophic Relationships.- I. Peripheral Nervous System.- II. Central Nervous System.- D. Neurological Disorders Targeted for IGF Therapy.- I. Diabetic Neuropathy.- 1. Pathophysiology.- 2. Experimental Observations in Non-Primates.- a) IGF Activity in Experimental IDDM.- b) IGF Activity in Experimental NIDDM.- c) IGF Treatment Prevents Neuropathy.- d) Relationship of Disturbances in IGF Axis to Hyperglycemia, Hyperinsulinemia and Weight Loss.- 3. IGF Activity in Primates.- a) Diabetic Monkeys.- b) Clinical Diabetes.- II. Chemotherapy-Induced Neuropathy.- III. Amyotrophic Lateral Sclerosis (ALS).- IV. Stroke.- V. Alzheimer's Disease.- VI. Myotonic Dystrophy.- E. Pharmacological Considerations.- I. Routes of Administration.- II. Volume of Distribution and Daily Production.- III. Bound and Free IGF Pools.- IV. Elimination Half-Time.- V. Clinical Effects of Recombinant Human IGF-I.- 1. Normal Subjects.- 2. Patient Populations.- VI. Effects of Recombinant Human IGF-II.- F. Concluding Comments.- References.- 6 Neurotrophic Factors in Peripheral Nerve Injury and Regeneration.- A. Introduction.- B. Causes of Peripheral Nerve Damage.- C. Symptoms and Pathophysiology of Peripheral-Nerve Damage.- I. Sensory Neuropathies.- II. Motor Neuronopathies.- D. Current Approaches to Therapy.- I. Sensory Neuropathies.- 1. Surgery.- 2. Analgesic Drugs.- II. Motor Neuronopathies.- E. Methods for the Study of Peripheral Nerve Damage in Laboratory Animals.- I. Mechanical Injury.- II. Neurotoxins.- III. Diabetes.- IV. Hereditary Motor Neuronopathies in Mice.- F. Endpoints Used to Assess Peripheral Nerve Regeneration In Vivo.- I. Quantitative Morphometric Analysis.- II. Functional Assays of Nerve Regeneration Distance.- III. Assessing the Functional Innervation of Target Tissues.- G. Beneficial Effects of Neurotrophic Agents in Animal Models of Neuropathy.- I. Mechanical Nerve Injury.- II. Neurotoxins.- III. Diabetes.- IV. Motor Neuronopathy in Mice.- H. Drug-Development Issues.- I. Clinical Experience with Neurotrophic Factors.- J. Conclusions and Future Directions.- References.- 7 Nerve Growth Factor Treatment for Alzheimer's Disease: The Experience of the First Attempt at Intracerebral Neurotrophic Factor Therapy.- A. Introduction.- B. Nerve Growth Factor as a Therapeutic Agent to Counteract Cholinergic Neuron Degeneration.- I. Cholinergic Neuron Atrophy in Alzheimer's Disease (AD).- II. Role of NGF in Cholinergic Neuron Development and Adult Function.- III. Pharmacological Effects of NGF in Animals with Experimental Cholinergic Deficits.- IV. Human Studies with NGF: Efficacy and Possible Adverse Effects.- V. Alternative Administration Strategies and Small-Molecule Mimetics.- C. Neurotrophic Factors for Non-Cholinergic Neurons Affected by the Disease.- D. Relationship to Alzheimer's Disease Pathology.- E. Conclusions.- References.- 8 Neurotrophic Roles of GDNF and Related Factors.- A. Introduction.- B. Molecular Structure of GDNF and Related Molecules.- I. Glial Cell Line-Derived Neurotrophic Factor.- II. Neurturin.- 1. Persephin.- C. Receptors and Signal Transduction of GDNF and Neurturin.- I. Ret.- 1. Molecular Structure and Signaling Pathways.- 2. Ret As a Functional Receptor for GDNF and Neurturin.- II. Additional Components of the Ret-Receptor Complex: ?1-and ?2-receptors.- 1. The GFR-al Receptor.- 2. The Neurturin-/TrnR2-/RTL2/GFR-?2-Receptor.- D. Distribution of GDNF, Neurturin and Their Receptors.- I. GDNF and Neurturin in the Nervous System.- II. GDNF and Neurturin in Non-Neural Tissues.- III. Expression of Ret, GFR-?1 and GFR-?2 in the Developing and Adult Nervous System.- IV. Expression of GDNF and its Receptors in the Lesioned Nervous System.- V. Expression of Ret, GFR-?1 and GFR-?2 Outside the Nervous System: Involvement of Ret in Neuroendocrine and Gastrointestinal Disorders.- E. Functions of GNDF and Neurturin in the Nervous System As Revealed In Vitro and In Vivo.- I. Glial Cell Line-Derived Neurotrophic Factor.- 1. GDNF and the Nigrostriatal Dopaminergic System.- a) Cultured Mesencephalic Cells.- b) Animal Models of Parkinsonism.- c) Effects in Unlesioned Animals.- 2. Other CNS Aminergic Neurons.- 3. GDNF and Intrinsic Striatal Neurons.- 4. Spinal Cord and Brainstem Motoneurons.- 5. Cerebellar Neurons.- 6. Sensory Neurons.- 7. Autonomic Neurons.- 8. Neural Crest.- 9. GDNF in CNS Lesion Models Other Than Parkinsonism.- II. Neurturin.- F. Developmental Roles of GDNF, Neurturin and Their Receptors As Revealed by Gene Targeting.- I. Glial Cell Line-Derived Neurotrophic Factor.- II. Ret.- III. Neurturin.- G. Perspectives.- I. Clinical Relevance.- II. Neurobiological Relevance.- References.- 9 Role of Neurotrophic Factors in Cerebral Ischemia.- A. Neurotrophic Factors, Their Receptors and Their Expression in the Central Nervous System (CNS).- I. Neurotrophic Factors Support Survival and Functionality of Neurons.- II. Neurotrophic-Factor Families.- 1. Neurotrophins.- 2. Glial-Derived Neurotrophic Factor (GDNF) and Transforming Growth Factors (TGFs).- 3. Ciliary Neurotrophic factor (CNTF), Fibroblast Growth Factors (FGFs), Insulin-Like Growth Factors (IGFs) and Other Factors.- III. Afferent Activity Regulates Neurotrophic Factor Expression.- B. Hypoxic-Ischemic Injury Regulates the Expression of Neurotrophic Factors and Their Receptors in the Central Nervous System.- I. Global Hypoxic-Ischemic Injury.- 1. Neurotrophins.- 2. Basic Fibroblast Growth Factor.- 3. IGFs, TGF-b and Other Factors.- II. Focal Hypoxic-Ischemic Injury.- 1. Neurotrophins.- 2. Basic Fibroblast Growth Factor.- 3. Other Factors.- C. Specific Growth Factors Can Attenuate Morphological and Functional Damage Caused by Hypoxic-Ischemic Brain Injury.- I. Global Ischemic Injury.- 1. Neurotrophins.- 2. Basic Fibroblast Growth Factor.- 3. TGF-b, IGF-I and Other Factors.- II. Focal Ischemic Injury.- 1. Neuroprotective Effects of Neurotrophins.- 2. Neuroprotective Effects of bFGF.- 3. Neuroprotective effects of IGF-I, TGF-? and Other Growth Factors.- 4. Protection Via Neurotrophic-Factor Induction.- D. Therapeutic Potential of Neurotrophic Factors in Hypoxic-Ischemic Brain Injury.- References.- 10 Strategies for Administering Neurotrophic Faetors to the Central Nervous System.- Abbreviations.- A. Introduction.- I. Characteristics of Neurotrophic Factors (NFs).- II. Rationale for Using NFs in Clinical Paradigms.- B. Administration of NFs to the Central Nervous System.- I. Delivery Issues.- C. Delivery Methods.- I. Delivery of NFs Using Mechanical-Release Devices.- 1. Systemic Delivery.- 2. Pumps.- 3. Slow Polymer-Release System.- II. Delivery of NFs Using Gene Therapy Approaches.- 1. In Vivo Gene Therapy.- a) Viral Vectors.- b) Adenoviral Vectors.- c) Adeno-Associated Viral Vectors.- d) Retroviral Vectors.- 2. Ex Vivo Gene Therapy.- a) Cell Grafting.- b) Encapsulation of Engineered Cell Lines.- D. Conclusion.- References.- 11 Neurotrophic Factor Mimetics.- A. Introduction.- B. Direct and Indirect Receptor Ligands.- I. Peptide Mimetics.- II. K-252a and Related Compounds that Modulate Trk Receptor Signalling.- III. Immunophilin Ligands.- IV. Others.- C. Regulators of Neurotrophic Factor Synthesis or Release.- I. Hormonal Regulation of Neurotrophin or Neurotrophin Receptor Expression.- II. Compounds Regulating Neurotrophin Synthesis.- D. Examples of Growth Hormone Secretagogues.- I. Discovery of L-692,429 and MK-0677.- II. The MK-0677 Receptor.- III. Clinical Use.- E. Conclusions.- References.


PRODUCT DETAILS

ISBN-13: 9783642641824
Publisher: Springer (Springer-Verlag Berlin and Heidelberg GmbH & Co. K)
Publication date: September, 2011
Pages: 343
Weight: 528g
Availability: Available
Subcategories: Neurology, Neuroscience, Pharmacology
Related books
From the same series

CUSTOMER REVIEWS

Average Rating