GAPDH binders as potential drugs for the therapy of polyglutamine diseases: design of a new screening assay.

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Article

Title:	GAPDH binders as potential drugs for the therapy of polyglutamine diseases: design of a new screening assay.
Authors:	Lazarev VF; Benken KA; Semenyuk PI; Sarantseva SV; Bolshakova OI; Mikhaylova ER; Muronetz VI; Guzhova IV; Margulis BA
Publication:	FEBS Lett. 2015 Feb 27;589(5):581-7. doi: 10.1016/j.febslet.2015.01.018. Epub 2015 Jan 24.
PubmedID	25625921
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.