| Literature DB >> 25625921 |
Vladimir F Lazarev1, Konstantin A Benken2, Pavel I Semenyuk3, Svetlana V Sarantseva4, Olga I Bolshakova4, Elena R Mikhaylova5, Vladimir I Muronetz3, Irina V Guzhova5, Boris A Margulis5.
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.Entities:
Keywords: Aggregation assay; Drug; Glyceraldehydes-3-phosphate dehydrogenase; Polyglutamine diseases; Small molecule; Therapeutic target; Transgenic Drosophila; Transglutaminase
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Year: 2015 PMID： 25625921 DOI： 10.1016/j.febslet.2015.01.018
Source DB: PubMed Journal: FEBS Lett ISSN： 0014-5793 Impact factor: 4.124