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.Full text not available from this repository.
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|
|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|
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