Curcumin-glucoside, a novel synthetic derivative of curcumin, inhibits α-synuclein oligomer formation: relevance to Parkinson's disease.
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.
Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore-570020.
Bharathi Shrikanth
BS
Gadad
Parvathy K
PK
Subramanya
Srinivas
S
Pullabhatla
Indi S
IS
Shantharam
K S
KS
Rao
D002151:Calorimetry / Q000379:methods; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005960:Glucosides / Q000737:chemistry*; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects; D012995:Solubility; D051844:alpha-Synuclein / Q000187:drug effects* / Q000378:metabolism
D005960:Glucosides; D051844:alpha-Synuclein; D003474:Curcumin