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Huntingtin-Associated Proteins

  • Chapter
Molecular Mechanisms of Neurodegenerative Diseases

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

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Abstract

Huntington’s disease (HD), with its writhing dancelike movements (chorea) and cardinal loss of neurons in the striatum (1), is the result of an unstable expanded CAG trinucleotide repeat that lengthens a variable glutamine tract in a novel protein called huntingtin (HD) (2). HD shares elements of a common pathogenic mechanism with at least seven other inherited neurodegenerative diseases, including spinobulbar muscular atrophy (SBMA) (3), dentatorubral-pallidoluysian atrophy (DRPLA/Haw River syndrome) (4–6), and several spinocerebellar ataxias (SCA1, SCA2, SCA3/MJD, SCA6 and SCA7) (7–14) (Fig. 1). Expanded glutamine segments in otherwise unrelated proteins cause specific neuronal cell loss in each case, suggesting unique protein context-dependent modulation of some intrinsic toxic property of polyglutamine (15–17). In this view, some feature of huntingtin produces HD pathology by presenting the embedded toxic glutamine tract to cells in a manner that culminates in a graded loss of striatal neurons. One molecular possibility is a glutamine-induced conformational change that alters huntingtin’s association with its normal or abnormal protein partners (18,19).

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Authors
  1. Marcy E. MacDonald
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  2. Lucius Passani
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  3. Paige Hilditch-Maguire
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MacDonald, M.E., Passani, L., Hilditch-Maguire, P. (2001). Huntingtin-Associated Proteins. In: Molecular Mechanisms of Neurodegenerative Diseases. Contemporary Clinical Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-006-3_15

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  • DOI: https://doi.org/10.1007/978-1-59259-006-3_15

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-197-4

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