NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
In 1993, the genetic mutation responsible for Huntington’s disease (HD) was identified. Considered a milestone in human genomics, this discovery has led to nearly two decades of remarkable progress that has greatly increased our knowledge of HD, and documented an unexpectedly large and diverse range of biochemical and genetic perturbations that seem to result directly from the expression of the mutant huntingtin gene.
Neurobiology of Huntington’s Disease: Applications to Drug Discovery presents a thorough review of the issues surrounding drug discovery and development for the treatment of this paradigmatic neurodegenerative disease. Drawing on the expertise of key researchers in the field, the book discusses the basic neurobiology of Huntington’s disease and how its monogenic nature confers enormous practical advantages for translational research, including the creation of robust experimental tools, models, and assays to facilitate discovery and validation of molecular targets and drug candidates for HD. Written to support future basic research as well as drug development efforts, this volume:
- Covers the latest research approaches in genetics, genomics, and proteomics, including high-throughput and high-content screening
- Highlights advances in the discovery and development of new drug therapies for neurodegenerative disorders
- Examines the practical realities of preclinical testing, clinical testing strategies, and, ultimately, clinical usage
While the development of effective drug treatments for Huntington’s disease continues to be tremendously challenging, a highly interactive and cooperative community of researchers and clinical investigators now brings us to the threshold of potential breakthroughs in the quest for therapeutic agents. The impressive array of drug discovery resources outlined in the text holds much promise for treating this devastating disease, providing hope to long-suffering Huntington’s disease patients and their families.
Contents
- Series Preface
- Preface
- Editors
- Contributors
- 1. Huntington’s Disease: Clinical Features and Routes to TherapyHenry L. Paulson and Roger L. Albin.
- 2. Huntington’s Disease Pathogenesis: Mechanisms and PathwaysAlbert R. La Spada, Patrick Weydt, and Victor V. Pineda.
- INTRODUCTION
- PROTEIN AGGREGATION AND DEGRADATION
- PROTEOLYTIC CLEAVAGE
- TRANSCRIPTIONAL DYSREGULATION
- EVIDENCE FOR MITOCHONDRIAL ABNORMALITIES AND DEFECTIVE ENERGY METABOLISM IN HD
- NEUROTROPHIC FACTORS
- CYTOSKELETAL DEFECTS AND AXONAL TRANSPORT
- A ROLE FOR THE LOSS OF HUNTINGTIN NORMAL FUNCTION IN HD?
- NON-CELL AUTONOMOUS DEGENERATION IN HD
- NEUROINFLAMMATION IN HD: HOW IMPORTANT ARE MICROGLIA?
- CONCLUSIONS
- REFERENCES
- 3. Protein Interactions and Target Discovery in Huntington’s DiseaseJohn P. Miller and Robert E. Hughes.
- INTRODUCTION
- PROTEIN INTERACTIONS IMPLICATE MECHANISMS AND TARGET PATHWAYS IN HD
- TECHNOLOGIES FOR DETECTION OF PROTEIN INTERACTIONS AND PROTEIN COMPLEXES
- LARGE-SCALE INTERACTION NETWORKS AND NEXT-GENERATION DATA MINING
- TRANSCRIPTION PROTEIN INTERACTIONS WITH HUNTINGTIN
- POTENTIAL PROSURVIVAL PROTEIN INTERACTIONS WITH NORMAL HUNTINGTIN
- POTENTIAL DETRIMENTAL INTERACTION PARTNERS OF MUTANT HUNTINGTIN
- TRANSCRIPTION PROTEIN INTERACTION SUMMARY
- REFERENCES
- 4. Target Validation for Huntington’s DiseaseSeung P. Kwak, James K. T. Wang, and David S. Howland.
- 5. High-Throughput and High-Content Screening for Huntington’s Disease TherapeuticsHemant Varma, Donald C. Lo, and Brent R. Stockwell.
- 6. Value of Invertebrate Genetics and Biology to Develop Neuroprotective and Preventive Medicine in Huntington’s DiseaseChristian Neri.
- 7. Mouse Models for Validating Preclinical Candidates for Huntington’s DiseaseX. William Yang and Michelle Gray.
- 8. Pharmaceutical Development for Huntington’s DiseaseRichard J. Morse, Janet M. Leeds, Douglas Macdonald, Larry Park, Leticia Toledo-Sherman, and Robert Pacifici.
- 9. RNA- and DNA- Based Therapies for Huntington’s DiseaseSass Meghan and Aronin Neil.
- 10. Recombinant Intrabodies as Molecular Tools and Potential Therapeutics for Huntington’s DiseaseKhoshnan Ali, Amber L. Southwell, Charles W. Bugg, Jan C. Ko, and Paul H. Patterson.
- INTRODUCTION
- STRATEGIES FOR INTRABODY CONSTRUCTION
- DEVELOPMENT OF EPITOPE-SPECIFIC INTRABODIES AGAINST HUNTINGTIN
- INTRABODIES AS RESEARCH TOOLS TO DISSECT MECHANISMS OF HTT DISEASE PATHOGENESIS
- NOVEL TARGETS FOR INTRABODY THERAPY IN HD
- DELIVERY OF INTRABODIES TO THE HD BRAIN
- FUTURE DIRECTIONS FOR INTRABODIES IN HD THERAPY
- REFERENCES
- 11. Biomarkers to Enable the Development of Neuroprotective Therapies for Huntington’s DiseaseSteven M. Hersch and H. Diana Rosas.
- 12. Huntington’s Disease: Clinical Experimental TherapeuticsDorsey E. Ray and Shoulson Ira.
This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint.
- NLM CatalogRelated NLM Catalog Entries
- Review High-Throughput and High-Content Screening for Huntington’s Disease Therapeutics.[Neurobiology of Huntington's D...]Review High-Throughput and High-Content Screening for Huntington’s Disease Therapeutics.Varma H, Lo DC, Stockwell BR. Neurobiology of Huntington's Disease: Applications to Drug Discovery. 2011
- Review Biomarkers to Enable the Development of Neuroprotective Therapies for Huntington’s Disease.[Neurobiology of Huntington's D...]Review Biomarkers to Enable the Development of Neuroprotective Therapies for Huntington’s Disease.Hersch SM, Rosas HD. Neurobiology of Huntington's Disease: Applications to Drug Discovery. 2011
- Review Value of Invertebrate Genetics and Biology to Develop Neuroprotective and Preventive Medicine in Huntington’s Disease.[Neurobiology of Huntington's D...]Review Value of Invertebrate Genetics and Biology to Develop Neuroprotective and Preventive Medicine in Huntington’s Disease.Neri C. Neurobiology of Huntington's Disease: Applications to Drug Discovery. 2011
- Review Protein Interactions and Target Discovery in Huntington’s Disease.[Neurobiology of Huntington's D...]Review Protein Interactions and Target Discovery in Huntington’s Disease.Miller JP, Hughes RE. Neurobiology of Huntington's Disease: Applications to Drug Discovery. 2011
- Review Genetic modifiers of Huntington's disease.[Mov Disord. 2014]Review Genetic modifiers of Huntington's disease.Gusella JF, MacDonald ME, Lee JM. Mov Disord. 2014 Sep 15; 29(11):1359-65. Epub 2014 Aug 25.
- Neurobiology of Huntington's DiseaseNeurobiology of Huntington's Disease
- Gene Links for PubMed (Select 2879243) (4)Gene
- MedGen for PubMed (Select 22791750) (4)MedGen
- Biomarkers to Enable the Development of Neuroprotective Therapies for Huntington...Biomarkers to Enable the Development of Neuroprotective Therapies for Huntington’s Disease - Neurobiology of Huntington's Disease
- PubChem Compound for PubMed (Select 21383448) (11)PubChem Compound
Your browsing activity is empty.
Activity recording is turned off.
See more...