Bioenergetics in Huntington's Disease

Authors

  • THOMAS GRÜNEWALD,

    1. Department of neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York 10021, USA
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  • M. FLINT BEAL

    Corresponding author
    1. Department of neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York 10021, USA
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Address for correspondence: M. Flint Beal, M.D., New York Presbyterian Hospital/Weill Medical College of Cornell University, Department of Neurology and Neuroscience, 525 East 68th Street, Room A569, New York, New York 10021. Phone: 212-746-6575; fax: 212-746-8532. e-mail: fbeal@mail.med.cornell.edu

Abstract

ABSTRACT: Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder with relentless course and prototypical clinical symptoms. In 1993 HD was associated with an expanded CAG triplet repeat stretch on chromosome 4 in the coding region of its target protein, huntingtin. The length of the resulting polyglutamine extensions correlates with lower age of onset and a higher density of ubiquitine-positive neuronal intranuclear inclusions. Recently it has been proposed that mutant huntingtin induces progressive neuronal cell death by an apoptotic mechanism. There is strong evidence that disturbances in cellular energy homeostasis and oxidative damage contribute to neurodegeneration. This review will summarize and discuss the current concepts that point towards an involvement of free radical-induced oxidative stress, glutamate excitotoxicity and mitochondrial resporatory chain defects in pathogenesis of HD.

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