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Replicating Huntington Disease’s Phenotype in Nonhuman Primates

  • Chapter
Central Nervous System Diseases

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Huntington’s disease (HD) is an inherited, autosomal dominant, neurodegenerative disorder characterized by involuntary choreiform movements, cognitive decline, and a progressive neuronal degeneration primarily affecting the striatum. At present there is no effective therapy, even palliative, against this disorder. The gene responsible for the disease has been localized on the short arm of chromosome 4 (1) and the molecular defect recently identified (2) as an abnormal repeat of CAG triplets in the 5′ coding region of a gene (IT15) encoding a protein (huntingtin) with unknown function. Despite the intense search for a cell pathology attached to this molecular defect, the mechanisms leading to neurodegeneration in HD still remain largely speculative (3). Nevertheless, recent studies have suggested that abnormal interactions between the mutated huntingtin and other proteins could be involved in the pathogenesis of HD. Thus, huntingtin has been shown to interact with several proteins including a cytoplasmic protein that associates with microtubules, mitochondria, and synaptic vesicles (HAP-1, 4), glyceraldehyde phosphate dehydrogenase (GAPDH, 5), an unidentified calmodulinassociated protein (6), a ubiquitin-associated protein (HIP-2, 7), and a protein homologous to the yeast cytoskeleton-associated protein sla2p (HIP-1, 8). These observations suggest that alterations in glycolysis, vesicle trafficking, or apoptosis could all be pathological mechanisms involved in HD. However, direct and indirect evidence for defects in mitochondrial energy metabolism (complex II–III deficiency) has been increasingly compelling over the past decade (9–15).

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Authors
  1. Philippe Hantraye
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  2. Stéphane Palfi
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  3. Vincent Mittoux
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  4. Caroline Dautry
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  5. Françoise Condé
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  6. Emmanuel Brouillet
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Editors and Affiliations

  1. Alkermes, Inc., Cambridge, MA, USA

    Dwaine F. Emerich PhD (Director of Neuroscience) (Director of Neuroscience)

  2. Department of Neuroscience, Alkermes, Inc., Cambridge, MA, USA

    Reginald L. Dean III MS

  3. University of South Florida College of Medicine, Tampa, FL, USA

    Paul R. Sanberg PhD, DSc

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Hantraye, P., Palfi, S., Mittoux, V., Dautry, C., Condé, F., Brouillet, E. (2000). Replicating Huntington Disease’s Phenotype in Nonhuman Primates. In: Emerich, D.F., Dean, R.L., Sanberg, P.R. (eds) Central Nervous System Diseases. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-691-1_17

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  • DOI: https://doi.org/10.1007/978-1-59259-691-1_17

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-152-3

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