Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection (Heat Shock Proteins, 3)

With the prevalence of neurodegenerative diseases on the rise as average life expectancy increases, the hunt for effective treatments and preventive measures for these disorders is a pressing challenge. Neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis have been termed ‘protein misfolding disorders'that are char- terized by the neural accumulation of protein aggregates. Manipulation of the cellular stress response involving the induction of heat shock proteins offers a the- peutic strategy to counter conformational changes in neural proteins that trigger pathogenic cascades resulting in neurodegenerative diseases. Heat shock proteins are protein repair agents that provide a line of defense against misfolded, aggregati- prone proteins. Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection reviews current progress on neural heat shock proteins (HSP) in relation to neurodegenerative diseases (Part I), neuroprotection (Part II), ext- cellular HSP (Part III) and aging and control of life span (Part IV). Key basic and clinical research laboratories from major universities and hospitals around the world contribute chapters that review present research activity and importantly project the field into the future. The book is a must read for researchers, postdoctoral fellows and graduate students in the fields of Neuroscience, Neurodegenerative Diseases, Molecular Medicine, Aging, Physiology, Pharmacology and Pathology. Table of Contents......Page 7 Preface......Page 10 List of Contributors......Page 11 PART I: Heat Shock Proteins and Neurodegenerative Diseases......Page 15 1. Chaperones and Polyglutamine Expansion Disorders......Page 16 2. Heat Shock Proteins, Unfolded Protein Response Chaperones and Alzheimer's Disease......Page 37 3. Cellular and Molecular Mechanisms Underlying Parkinson's Disease: The Role of Molecular Chaperones......Page 63 4. Heat Shock Proteins as Therapeutic Targets in Amyotrophic Lateral Sclerosis......Page 81 5. The Role of Chaperones and Co-Chaperones in Retinal Degenerative Diseases......Page 120 6. Neuroprotective Features of Hsp90 Inhibitors Exhibiting Anti-Inflammatory Actions: Implications for Multiple Sclerosis......Page 135 7. Role of HspB1 and HspB8 in Hereditary Peripheral Neuropathies: Beyond the Chaperone Function......Page 148 PART II: Heat Shock Proteins and Neuroprotection......Page 165 8. Heat Shock Proteins Hsp70 and Hsp27 and Neural Cellular Protection......Page 166 9. Molecular Chaperones and Protection in Animal and Cellular Models of Ischemic Stroke......Page 185 10. Strategies for Conferring Neuroprotection and Countering the High Threshold for Induction of the Stress Response in Motor Neurons......Page 208 11. Use of Viral Gene Delivery Systems to Investigate the Neuroprotective Roles of Hsp70 and Hsp40 Proteins......Page 227 12. Heat Shock Proteins at the Synapse: Implications for Functional Protection of the Nervous System......Page 242 PART III: Extracellular Heat Shock Proteins and the Nervous System......Page 258 13. Release of Heat Shock Proteins and their Effects When in the Extracellular Space in the Nervous System......Page 259 14. Silencing of Metastasis-Associated Gene 1 (MTA1) Stimulates Hsp70 Cellular Release and Neurite Extension......Page 275 15. Extracellular Chaperones and Amyloids......Page 285 PART IV: Aging, Control of Life Span and Expression of Heat Shock Proteins......Page 318 16. Neural Expression of Small Heat Shock Proteins Influences Longevity and Resistance to Oxidative Stress......Page 319 17. Mechanistic Links Between Aging and Aggregation-Mediated Proteotoxicity: Role of HSF-1 and DAF-16......Page 337 18. Protein Quality Control and Heat Shock Gene Expression in the Nervous System......Page 349 19. Serum Hsp70 Level as a Biomarker of Exceptional Longevity......Page 365 G......Page 372 P......Page 373 V......Page 374 With the prevalence of neurodegenerative diseases on the rise as average life expectancy increases, the hunt for effective treatments and preventive measures for these disorders is a pressing challenge. Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis have been termed 'protein misfolding disorders' that are characterized by the neural accumulation of protein aggregates. Manipulation of the cellular stress response involving the induction of heat shock proteins offers a therapeutic strategy to counter conformational changes in neural