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A huntingtin-associated protein enriched in brain with implications for pathology

Nature volume 378, pages 398402 (23 November 1995) | Download Citation

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Abstract

HUNTINGTON's disease (HD) is an autosomal dominant neuro-degenerative disorder caused by an expanding polyglutamine repeat in the IT 15 or huntingtin gene1. Although this gene is widely expressed2–9 and is required for normal development10–12, the pathology of HD is restricted to the brain, for reasons that remain poorly understood. The huntingtin gene product is expressed at similar levels in patients and controls, and the genetics of the disorder13,14 suggest that the expansion of the polyglutamine repeat induces a toxic gain of function, perhaps through interactions with other cellular proteins15–18. Here we report the identification of a protein (huntingtin-associated protein (HAP)-l) that binds to huntingtin. This binding is enhanced by an expanded polyglutamine repeat, the length of which is also known to correlate with the age of disease onset19–21. The HAP-1 protein is enriched in the brain, suggesting a possible basis for the selective brain pathology of HD.

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Author information

Affiliations

  1. Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

    • Xiao-Jiang Li
    • , Shi-Hua Li
    • , Alan H. Sharp
    • , Frederick C. Nucifora
    • , Gabriele Schilling
    •  & Christopher A. Ross
  2. Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

    • Xiao-Jiang Li
    • , Shi-Hua Li
    • , Alan H. Sharp
    • , Frederick C. Nucifora
    • , Gabriele Schilling
    • , Solomon H. Snyder
    •  & Christopher A. Ross
  3. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

    • Xiao-Jiang Li
    • , Shi-Hua Li
    • , Anthony Lanahan
    • , Paul Worley
    • , Solomon H. Snyder
    •  & Christopher A. Ross
  4. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

    • Anthony Lanahan
    •  & Paul Worley

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https://doi.org/10.1038/378398a0

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