Neurobiology of Huntington’s Disease : Applications to Drug Discovery book cover
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Neurobiology of Huntington’s Disease
Applications to Drug Discovery





ISBN 9781138116627
Published November 15, 2017 by CRC Press
338 Pages 36 B/W Illustrations

 
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Book Description

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.

Table of Contents

Huntington’s Disease: Clinical Features and Routes to Therapy, Henry L. Paulson and Roger L. Albin
Huntington’s Disease Pathogenesis: Mechanisms and Pathways, Albert R. La Spada, Patrick Weydt, and Victor V. Pineda
Protein Interactions and Target Discovery in Huntington’s Disease, John P. Miller and Robert E. Hughes
Target Validation for Huntington’s Disease, Seung P. Kwak, James K. T. Wang, and David S. Howland
High-Throughput and High-Content Screening for Huntington’s Disease Therapeutics, Hemant Varma, Donald C. Lo, and Brent R. Stockwell
Value of Invertebrate Genetics and Biology to Develop Neuroprotective and Preventive Medicine in Huntington’s Disease, Christian Neri
Mouse Models for Validating Preclinical Candidates for Huntington’s Disease, X. William Yang and Michelle Gray
Pharmaceutical Development for Huntington’s Disease, Richard J. Morse, Janet M. Leeds, Douglas Macdonald, Larry Park, Leticia Toledo-Sherman, and Robert Pacifici
RNA- and DNA-Based Therapies for Huntington’s Disease, Meghan Sass and Neil Aronin
Recombinant Intrabodies as Molecular Tools and Potential Therapeutics for Huntington’s Disease, Ali Khoshnan, Amber Southwell, Charles W. Bugg, Jan C. Ko, and Paul H. Patterson
Biomarkers to Enable the Development of Neuroprotective Therapies for Huntington’s Disease, Steven M. Hersch and H. Diana Rosas
Huntington’s Disease, E. Ray Dorsey and Ira Shoulson

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Reviews

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