Letter | Published:

Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxias

Nature volume 378, pages 403406 (23 November 1995) | Download Citation

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Abstract

A POLYGLUTAMINE expansion (encoded by a CAG repeat) in specific proteins causes neurodegeneration in Huntington's disease (HD) and four other disorders1–6, by an unknown mechanism thought to involve gain of function or toxicity of the mutated protein7,8. The pathological threshold is 37–40 glutamines in three of these diseases, whereas the corresponding normal proteins contain polymorphic repeats of up to about 35 glutamines1–3. The age of onset of clinical manifestations is inversely correlated to the length of the polyglutamine expansion. Here we report the characterization of a monoclonal antibody that selectively recognizes polyglutamine expansion in the proteins implicated in HD and in spinocerebellar ataxia (SCA) 1 and 3. The intensity of signal depends on the length of the polyglutamine expansion, and the antibody also detects specific pathological proteins expected to contain such expansion, in SCA2 and in autosomal dominant cere-bellar ataxia with retinal degeneration, whose genes have not yet been identified9–13.

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Author information

Affiliations

  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS, INSERM, ULP, B.P. 163, 67404 Illkirch Cédex, France

    • Yvon Trottier
    • , Yves Lutz
    • , Georges Imbert
    • , Didier Devys
    • , Frédéric Saudou
    • , Chantal Weber
    • , Laszlo Tora
    • , Alexis Brice
    •  & Jean-Louis Mandel
  2. INSERM U.289, Hôpital de la Salpêtrière, 75651 Paris Cedex 13,France

    • Giovanni Stevanin
    • , Géraldine Cancel
    • , Gilles David
    •  & Yves Agid

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https://doi.org/10.1038/378403a0

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