Neurobiology of Huntington's Disease: Applications to Drug Discovery / Edition 1

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Overview

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.

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Editorial Reviews

From the Publisher
The book is written lucidly by authorities in their respective fields, covering clinical features, pathogenic mechanisms, protein interactions, preclinical models, biomarkers, small molecules and other approaches (eg, recombinant antibodies), screening strategies, and drug development. Informative figures and tables are provided, and reproduction of key figures as a set of colour plates provides a useful centrepiece. One unifying message is that the polyglutamine xpansion leads to a complex cascade of diverse molecular and cellular events, the progress of which is difficult to slow or halt. Innovative approaches described, such as the target validation process of the Cure Huntington's Disease Initiative (CHDI) Foundation, will be of interest to those studying other neurological diseases.
—Anthony J Hannan, writing in The Lancet Neurology, March 2011
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Product Details

  • ISBN-13: 9780849390005
  • Publisher: Taylor & Francis
  • Publication date: 7/1/2010
  • Series: Frontiers in Neuroscience Series
  • Edition number: 1
  • Pages: 338
  • Product dimensions: 6.40 (w) x 9.40 (h) x 0.90 (d)

Table of Contents

Series Preface

Preface

Editors

Contributors

Chapter 1 Huntington's Disease: Clinical Features and Routes to Therapy Roger L. Albin Albin, Roger L. 1

Chapter 2 Huntington's Disease Pathogenesis: Mechanisms and Pathways Victor V. Pineda Pineda, Victor V. 29

Chapter 3 Protein Interactions and Target Discovery in Huntington's Disease Robert E. Hughes Hughes, Robert E. 55

Chapter 4 Target Validation for Huntington's Disease David S. Howland Howland, David S. 85

Chapter 5 High-Throughput and High-Content Screening for Huntington's Disease Therapeutics Brent R. Stockwell Stockwell, Brent R. 121

Chapter 6 Value of Invertebrate Genetics and Biology to Develop Neuroprotective and Preventive Medicine in Huntington's Disease Christian Neri Neri, Christian 147

Chapter 7 Mouse Models for Validating Preclinical Candidates for Huntington's Disease Michelle Gray Gray, Michelle 165

Chapter 8 Pharmaceutical Development for Huntington's Disease Robert Pacifici Pacifici, Robert 197

Chapter 9 RNA- and DNA-Based Therapies for Huntington's Disease Neil Aronin Aronin, Neil 225

Chapter 10 Recombinant Intrabodies as Molecular Tools and Potential Therapeutics for Huntington's Disease Paul H. Patterson Patterson, Paul H. 255

Chapter 11 Biomarkers to Enable the Development of Neuroprotective Therapies for Huntington's Disease H. Diana Rosas Rosas, H. Diana 267

Chapter 12 Huntington's Disease: Clinical Experimental Therapeutics Ira Shoulson Shoulson, Ira 285

Index 299

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