ИСТИНА

A prion protein is a membrane-bound protein of neural tissue, which plays a crucial role in the development of a number of amyloid diseases, such as syndrome Kreutzfeldt-Jacobs, fatal familial insomnia, Kuru, scrapie and others. The interaction of the infectious prion with native prion protein amyloid causes its transformation and the subsequent accumulation of amyloid fibrils that causes the development of neurodegeneration. The aim of our work was to study the effect of glycation of prion protein to its ability to form toxic oligomers and fibrils to clarify the relationship between disorders of carbohydrate metabolism (first of all, occurring in diabetes) on the development of prion amyloidoses. We modified recombinant ovine prion protein by glucose and methylglyoxal. Most effective glycation of lysyl residues occurred in case of methylglyoxal. In itself, glycation does not lead to the aggregation of prion protein; however, it causes an increase in fluorescence thioflavin T, which is specific dye for detection of amyloid structure. We studied the effect of glycation on the processes of oligomerization and aggregation of prion protein. We also investigated the effect of prions (native, glycated, and also oligomers and fibrils) on the system of chaperones, using bacterial chaperonin complex GroEL/GroES. Chaperone-dependent reactivation of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was blocked by monomeric form of the prion. PrP oligomers slow down chaperone-dependent reactivation of GAPDH, and the PrP fibrils do not affect this process. Chaperonin complex GroEL/GroES can simultaneously bind GAPDH and different forms of prion protein PrP. Thus, we have shown that glycation of prion protein, which can occur at elevated concentrations of glucose and other sugars in the blood, significantly alters the efficiency of amyloid transformation and can affect the development of prion amyloidoses. This work was supported by Russian Scientific Foundation (grant № 16-14-10027).