Polyglutamine expansion as a pathological epitope in Huntington’s disease and four dominant cerebellar ataxias.
Nature. 1995-11-01; 378(6555): 403-406
DOI: 10.1038/378403a0
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1. Nature. 1995 Nov 23;378(6555):403-6.
Polyglutamine expansion as a pathological epitope in Huntington’s disease and
four dominant cerebellar ataxias.
Trottier Y(1), Lutz Y, Stevanin G, Imbert G, Devys D, Cancel G, Saudou F, Weber
C, David G, Tora L, et al.
Author information:
(1)Institut de Génétique et de Biologie Moléculaire et Cellulaire (GBMC), CNRS,
INSERM, Illkirch, France.
A polyglutamine expansion (encoded by a CAG repeat) in specific proteins causes
neurodegeneration in Huntington’s disease (HD) and four other disorders, by an
unknown mechanism thought to involve gain of function or toxicity of the mutated
protein. 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 glutamines. 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
cerebellar ataxia with retinal degeneration, whose genes have not yet been
identified.
DOI: 10.1038/378403a0
PMID: 7477379 [Indexed for MEDLINE]