Huntington disease: new insights into the relationship between CAG expansion and disease

Jamal Nasir, Y Paul Goldberg, Michael R Hayden

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    The mutation underlying Huntington disease (HD) is CAG expansion beyond 35 repeats within a novel gene. Recently, new insights into the role of the HD protein (huntingtin) in the pathogenesis of HD have emerged. The CAG is translated and expression of mutant huntingtin is essential for neuronal death. Huntingtin is crucial for normal development and may be regarded as a cell survival gene. Huntingtin is specifically cleaved during apoptosis by a key cysteine protease, apopain, known to play a pivotal role in apoptotic cell death. The rate of cleavage is enhanced by longer polyglutamine tracts, suggesting that inappropriate apoptosis underlies HD. Recently, three proteins have been identified and have been shown specifically to interact with huntingtin, two of these interactions being influenced by CAG length. Several different approaches to develop an animal model for HD include cDNA and YAC transgenics, as well as 'knock-in' strategies. Such a model will be critical for the understanding of the natural history of HD and for the testing of new therapeutic modalities.
    Original languageEnglish
    Pages (from-to)1431-1435
    Number of pages5
    JournalHuman Molecular Genetics Review
    Volume5
    DOIs
    Publication statusPublished - 1996

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    Huntington Disease
    Apoptosis
    Cysteine Proteases
    Caspase 3
    Genes
    Cell Survival
    Cell Death
    Animal Models
    Complementary DNA
    Mutation
    Proteins

    Cite this

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    title = "Huntington disease: new insights into the relationship between CAG expansion and disease",
    abstract = "The mutation underlying Huntington disease (HD) is CAG expansion beyond 35 repeats within a novel gene. Recently, new insights into the role of the HD protein (huntingtin) in the pathogenesis of HD have emerged. The CAG is translated and expression of mutant huntingtin is essential for neuronal death. Huntingtin is crucial for normal development and may be regarded as a cell survival gene. Huntingtin is specifically cleaved during apoptosis by a key cysteine protease, apopain, known to play a pivotal role in apoptotic cell death. The rate of cleavage is enhanced by longer polyglutamine tracts, suggesting that inappropriate apoptosis underlies HD. Recently, three proteins have been identified and have been shown specifically to interact with huntingtin, two of these interactions being influenced by CAG length. Several different approaches to develop an animal model for HD include cDNA and YAC transgenics, as well as 'knock-in' strategies. Such a model will be critical for the understanding of the natural history of HD and for the testing of new therapeutic modalities.",
    author = "Jamal Nasir and Goldberg, {Y Paul} and Hayden, {Michael R}",
    year = "1996",
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    language = "English",
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    Huntington disease: new insights into the relationship between CAG expansion and disease. / Nasir, Jamal; Goldberg, Y Paul; Hayden, Michael R.

    In: Human Molecular Genetics Review, Vol. 5, 1996, p. 1431-1435.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Huntington disease: new insights into the relationship between CAG expansion and disease

    AU - Nasir, Jamal

    AU - Goldberg, Y Paul

    AU - Hayden, Michael R

    PY - 1996

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    N2 - The mutation underlying Huntington disease (HD) is CAG expansion beyond 35 repeats within a novel gene. Recently, new insights into the role of the HD protein (huntingtin) in the pathogenesis of HD have emerged. The CAG is translated and expression of mutant huntingtin is essential for neuronal death. Huntingtin is crucial for normal development and may be regarded as a cell survival gene. Huntingtin is specifically cleaved during apoptosis by a key cysteine protease, apopain, known to play a pivotal role in apoptotic cell death. The rate of cleavage is enhanced by longer polyglutamine tracts, suggesting that inappropriate apoptosis underlies HD. Recently, three proteins have been identified and have been shown specifically to interact with huntingtin, two of these interactions being influenced by CAG length. Several different approaches to develop an animal model for HD include cDNA and YAC transgenics, as well as 'knock-in' strategies. Such a model will be critical for the understanding of the natural history of HD and for the testing of new therapeutic modalities.

    AB - The mutation underlying Huntington disease (HD) is CAG expansion beyond 35 repeats within a novel gene. Recently, new insights into the role of the HD protein (huntingtin) in the pathogenesis of HD have emerged. The CAG is translated and expression of mutant huntingtin is essential for neuronal death. Huntingtin is crucial for normal development and may be regarded as a cell survival gene. Huntingtin is specifically cleaved during apoptosis by a key cysteine protease, apopain, known to play a pivotal role in apoptotic cell death. The rate of cleavage is enhanced by longer polyglutamine tracts, suggesting that inappropriate apoptosis underlies HD. Recently, three proteins have been identified and have been shown specifically to interact with huntingtin, two of these interactions being influenced by CAG length. Several different approaches to develop an animal model for HD include cDNA and YAC transgenics, as well as 'knock-in' strategies. Such a model will be critical for the understanding of the natural history of HD and for the testing of new therapeutic modalities.

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