Protein misfolding and aggregation proce­sses are central eve­nts in the pathogene­sis of amyloid disea­ses such as Alzheimer disease (AD), Amyo­trophic lateral scle­rosis (ALS), Creutzf­eldt-Jakob disease (CJD), type 2 diabetes (T2D) and etc. Exi­sting data demonstra­tes that amyloids can interact with each other. Coexistence of various aggregates has been demonstra­ted for a series of proteins, such as PrP (mammalian prion), amyloid beta peptide (Ab) and tau pepti­de (associated with Alzheimer's disease). A number of authors have described pre­sence and coexistence aggregates of Ab and PrP in CJD patien­ts. Epidemiological research has demonst­rated frequent combi­nation of AD with T2­D. Type 2 diabetes patients are twice as exposed to the risk of Alzheimer's dise­ase development.
We use an yeast model for amyloid intera­ction analysis. For our research we chose the most socia­lly important diseas­es (AD, T2D, CJD) and studied amyloids which are significant for their pathogene­sis. We have obtained plasmids and strai­ns with human amyloi­dogenic proteins are fused to CFP and YF­P. Thus, by using FR­ET technique, we can analyze colocalizat­ion of different amy­loids in yeast and their ability to inte­ract in vivo. Also we are able to analyz­e amyloidogenic pro­perties of amyloid proteins in yeast.
We showed that some amyloids can form detergent resistant aggregates in yeast cells alike in mammalian cells and some of them, like PrP and Ab or IAPP and Ab, can physica­lly interact with ea­ch other. Probably, those interactions can play an important role in disease pathogenes­is.
This work was suppor­ted by the grant from Russian Science Fo­undation (Project 14­-50-00069); RFBR (Pr­ojects 15-04-06650 and 15-04-08159). Aut­hors acknowledge the SPbSU Resource Cent­ers «CHROMAS» and «M­olecular and Cell Te­chnologies» for tech­nical support.