ИСТИНА

Colocalization of glycolytic enzyme glyceraldehyde­3­phosphate dehydrogenase (GAPDH) with alpha­synuclein in Lewy bodies was demonstrated by immunofluorescent analysis in brain of patients with Parkinson’s disease. Co­expression of GAPDH and alpha­synuclein in COS­7 cells results in the formation of Lewy body­like inclusions, suggesting possible GAPDH involvement in Lewy body formation in synucleinopathies in vivo . However, there is still no direct evidence of the interaction between these proteins. Our molecular modeling data predicted the binding of alpha­synuclein to the positively charged groove in the tetrameric GAPDH molecule that comprises NAD + ­binding pocket. Direct interaction between alpha­synuclein and GAPDH was confirmed by different experimental approaches. It was shown that the binding of alpha­synuclein to partially oxidized GAPDH results in the inactivation of the enzyme, but does not lead to dissociation of the tetrameric GAPDH into dimers or monomers. At the same time, the addition of the partially oxidized GAPDH to alpha­synuclein prevents its amyloid transformation. Thus, the interaction between GAPDH and alpha­ synuclein could play a role in the onset and development of synucleinopathies. Further investigation of specific interaction between these two proteins could lead to better understanding pathogenetic mechanisms of synucleinopathies and help in searching for drug targets for prevention and curing of these disorders. Acknowledgments This work was supported by the Russian Science Foundation (project No. 16­14­10027).