Curcumin modulates ?-synuclein aggregation and toxicity.

ABSTRACT: In human beings, Parkinson's disease (PD) is associated with the oligomerization and amyloid formation of ?-synuclein (?-Syn). The polyphenolic Asian food ingredient curcumin has proven to be effective against a wide range of human diseases including cancers and neurological disorders. While curcumin has been shown to significantly reduce cell toxicity of ?-Syn aggregates, its mechanism of action remains unexplored. Here, using a series of biophysical techniques, we demonstrate that curcumin reduces toxicity by binding to preformed oligomers and fibrils and altering their hydrophobic surface exposure. Further, our fluorescence and two-dimensional nuclear magnetic resonance (2D-NMR) data indicate that curcumin does not bind to monomeric ?-Syn but binds specifically to oligomeric intermediates. The degree of curcumin binding correlates with the extent of ?-Syn oligomerization, suggesting that the ordered structure of protein is required for effective curcumin binding. The acceleration of aggregation by curcumin may decrease the population of toxic oligomeric intermediates of ?-Syn. Collectively; our results suggest that curcumin and related polyphenolic compounds can be pursued as candidate drug targets for treatment of PD and other neurological diseases.

SUBMITTER: Singh PK 

PROVIDER: S-EPMC3605819 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature