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

Bharathi Shrikanth Gadad, Parvathy K. Subramanya, Srinivas Pullabhatla, Indi S. Shantharam, K. S. Rao

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)76-84
Number of pages9
JournalCurrent Pharmaceutical Design
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • Aggregation
  • Alpha-synuclein
  • Curcumin-glucoside
  • Oligomer
  • Parkinson's disease

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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