Direct interaction between selenoprotein R and Aβ42

Amyloid-β (Aβ) peptides have taken a central role in AD research, the aggregation of Aβ peptide is involved in the progression of Alzheimer's disease (AD). The 35th amino acid was methionine (Met) in Aβ peptides and it's redox state is critical in determining the biological activity of Aβ. It has been suggested that oxidation of Met35 (Met35O) plays a key role in the formation of paranuclei and in the control of oligomerization pathway choice. As an antioxidative selenoenzyme, Selenoprotein R (SelR) plays important roles in reducing the R-form of MetO to Met to maintain intracellular redox balance. However, the relationship between SelR and Aβ was little investigated. Here, we found that SelR can directly interact with Aβ42, and the interaction between SelR and Aβ42 was verified by fluorescence resonance energy transfer (FRET), co-immunoprecipitation (co-IP), and pull-down assays. SelR is closely related to AD, its biological functions in human brain become a research focus. This work implies that SelR makes it capable of modulating Aβ42 aggregation and provides a novel avenue for further study on the mechanism of SelR in AD prevention.