Gadad, Bharathi Shrikanth and Subramanya, Parvathy K and Pullabhatla, Srinivas and Shantharam, Indi S and Rao, KS (2012) Curcumin-glucoside, A Novel Synthetic Derivative of Curcumin, Inhibits alpha-Synuclein Oligomer Formation: Relevance to Parkinson's Disease. In: Current Pharmaceutical Design, 18 (1). pp. 76-84.
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alpha-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 alpha-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 alpha-synuclein monomeric and oligomeric forms were characterized by micro-calorimetry. It was observed that titration of Curc-gluc with alpha-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 dose-dependent manner and enhanced alpha-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 alpha-synuclein oligomeric form and prevents further fibrillization of alpha-synuclein; this might aid the development of disease modifying agents in preventing or treating PD.
| Item Type: | Journal Article |
|---|---|
| Publication: | Current Pharmaceutical Design |
| Publisher: | Bentham Science Publishers |
| Additional Information: | Copyright of this article belongs to Bentham Science Publishers. |
| Keywords: | Alpha-synuclein;Parkinson's disease;curcumin-glucoside; oligomer;aggregation |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 13 Mar 2012 12:02 |
| Last Modified: | 22 May 2012 09:48 |
| URI: | http://eprints.iisc.ac.in/id/eprint/43860 |
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