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Lazarev, V.F., Benken, K.A., Semenyuk, P.I., Sarantseva, S.V., Bolshakova, O.I., Mikhaylova, E.R., Muronetz, V.I., Guzhova, I.V., Margulis, B.A. (2015). GAPDH binders as potential drugs for the therapy of polyglutamine diseases: Design of a new screening assay.  FEBS Lett. 589(5): 581--587.
FlyBase ID
FBrf0227599
Publication Type
Research paper
Abstract
Proteins with long polyglutamine repeats form a complex with glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which enhances aggregation and cytotoxicity in models of Huntington disease. The aim of this study was to develop a novel assay for the screening of anti-aggregation compounds with a focus on the aggregation-promoting capacity of GAPDH. The assay includes a pure Q58 polyglutamine fragment, GAPDH, and a transglutaminase that links the two proteins. The feasibility of the new assay was verified using two GAPDH binders, hydroxynonenal and -(-)deprenyl, and the benzothiazole derivative PGL-135 which exhibits anti-aggregation effect. All three substances were shown to reduce aggregation and cytotoxicity in the cell and in the fly model of Spinocerebellar ataxia.
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    FEBS Lett.
    Title
    FEBS Letters
    Publication Year
    1968-
    ISBN/ISSN
    0014-5793
    Data From Reference
    Alleles (2)
    Genes (2)
    Human Disease Models (2)
    Insertions (1)