Blocking the Thiol at Cysteine-322 Destabilizes Tau Protein and Prevents Its Oligomer Formation
2018-05-01T00:00:00Z (GMT) by
Abnormal accumulation of tau protein into oligomers contributes to neuronal dysfunction. Reduction of tau level is potentially able to prevent its accumulation. Here we uncover a critical role of the free thiol at Cys-322 in determining tau stability. We found that the application of thiol-blocking agents like NEM or MMTS blocks this thiol, by which it destabilizes tau protein and prevents its oligomer formation. Furthermore, we identified a tau-interacting protein, selenoprotein W, which attenuates tau accumulation by forming disulfide linkage between SelW Cys-37 and tau Cys-322. These findings provide a promising strategy to prevent tau accumulation and oligomer formation.
CC BY-NC 4.0