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

Abstract:

: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.

journal_name

Curr Pharm Des

authors

Gadad BS,Subramanya PK,Pullabhatla S,Shantharam IS,Rao KS

doi

10.2174/138161212798919093

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

76-84

issue

1

eissn

1381-6128

issn

1873-4286

pii

BSP/CPD/E-Pub/000804

journal_volume

18

pub_type

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