Curcumin-glucoside, a novel synthetic derivative of curcumin, inhibits α-synuclein oligomer formation: relevance to Parkinson's disease

• Published in: Current pharmaceutical design Vol. 18; no. 1; p. 76
• Main Authors: Gadad, Bharathi Shrikanth, Subramanya, Parvathy K, Pullabhatla, Srinivas, Shantharam, Indi S, Rao, K S
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 2012
• Subjects: alpha-Synuclein - drug effects; alpha-Synuclein - metabolism; Calorimetry - methods; Curcumin - administration & dosage; Curcumin - chemistry; Curcumin - pharmacology; Dose-Response Relationship, Drug; Drug Design; Glucosides - chemistry; Parkinson Disease - drug therapy; Parkinson Disease - physiopathology; Parkinson Disease - prevention & control; Protein Binding; Protein Multimerization - drug effects; Solubility
• ISSN: 1873-4286
• DOI: 10.2174/138161212798919093

α-Synuclein aggregation is centrally implicated in Parkinson's disease (PD). It involves multi-step nucleated polymerization process via the formation of dimers, soluble toxic oligomers and insoluble fibrils. In the present study, we synthesized a novel compound viz., Curcumin-glucoside (Curc-gluc), a modified form of curcumin and studied its anti-aggregating potential with α-synuclein. Under aggregating conditions in vitro, Curc-gluc prevents oligomer formation as well as inhibits fibril formation indicating favorable stoichiometry for inhibition. The binding efficacies of Curc-gluc to both α-synuclein monomeric and oligomeric forms were characterized by micro-calorimetry. It was observed that titration of Curc-gluc with α-synuclein monomer yielded very low heat values with low binding while, in case of oligomers, Curc-gluc showed significant binding. Addition of Curc-gluc inhibited aggregation in a dosedependent manner and enhanced α-synuclein solubility, which propose that Curc-gluc solubilizes the oligomeric form by disintegrating preformed fibrils and this is a novel observation. Overall, the data suggest that Curc-gluc binds to α-synuclein oligomeric form and prevents further fibrillization of α-synuclein; this might aid the development of disease modifying agents in preventing or treating PD.