Acceleration of oxidative protein folding by curcumin through novel non-redox chemistry.

Curcumin, the major constituent of turmeric is a known antioxidant. We have examined the oxidative folding of the model four-disulfide-bond-containing protein bovine pancreatic ribonuclease A (RNase A) in its presence; results indicate that RNase A regeneration rate increases in a curcumin-dependent manner. Examination of the native tendency of the fully-reduced polypeptide and the stability of key folding intermediates suggests that the increased oxidative folding rate can be attributed to native-like elements induced within the fully-reduced polypeptide and the stabilization of native-like species by this non-redox-active natural product. Our results provide a template for the design of curcuminoid-based synthetic small-molecule fold catalysts that accelerate the folding of ER-processed proteins; this assumes significance given that nitrosative stress and dysfunction of the ER-resident oxidoreductase protein disulfide isomerise due to S-nitrosylation are factors associated with the pathogenesis of Alzheimer's and Parkinson's diseases.