| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 10870277 | FEBS Letters | 2015 | 7 Pages |
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 â(â)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.
Keywords
AFMDARTSNPCHNEPolyQdrug affinity responsive target stabilityDEPTransgenic DrosophilaTTGPGLGAPDHGSTSDSPBSDLSHuntington diseasepolyglutamine diseasesTransglutaminaseTissue transglutaminaseDrugsodium dodecyl sulfatephosphate buffer salineLDHSmall moleculeatomic force microscopySpinocerebellar Ataxia Type 3Therapeutic targethydroxynonenalDynamic Light ScatteringPolyglutamineglutathione-S-transferaseglyceraldehydes-3-phosphate dehydrogenaseglyceraldehyde-3-phosphate dehydrogenase
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Authors
Vladimir F. Lazarev, Konstantin A. Benken, Pavel I. Semenyuk, Svetlana V. Sarantseva, Olga I. Bolshakova, Elena R. Mikhaylova, Vladimir I. Muronetz, Irina V. Guzhova, Boris A. Margulis,