title: Effect of curcumin analogs onα-synuclein aggregation and cytotoxicity.
abstract: Alpha-synuclein (α-Syn) aggregation into oligomers and fibrils is associated with dopaminergic neuron loss occurring in Parkinson's disease (PD) pathogenesis. Compounds that modulate α-Syn aggregation and interact with preformed fibrils/oligomers and convert them to less toxic species could have promising applications in the drug development efforts against PD. Curcumin is one of the Asian food ingredient which showed promising role as therapeutic agent against many neurological disorders including PD. However, the instability and low solubility makes it less attractive for the drug development. In this work, we selected various curcumin analogs and studied their toxicity, stability and efficacy to interact with different α-Syn species and modulation of their toxicity. We found a subset of curcumin analogs with higher stability and showed that curcumin and its various analogs interact with preformed fibrils and oligomers and accelerate α-Syn aggregation to produce morphologically different amyloid fibrils in vitro. Furthermore, these curcumin analogs showed differential binding with the preformed α-Syn aggregates. The present data suggest the potential role of curcumin analogs in modulating α-Syn aggregation.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400 076, India.
authors.forename: Narendra Nath
authors.initials: NN
authors.lastname: Jha
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400 076, India.
authors.forename: Dhiman
authors.initials: D
authors.lastname: Ghosh
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400 076, India.|IITB Monash Research Academy, Indian Institute of Technology Bombay, Mumbai 400 076, India.
authors.forename: Subhadeep
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400 076, India.
authors.forename: Arunagiri
authors.initials: A
authors.lastname: Anoop
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400 076, India.
authors.forename: Reeba S
authors.initials: RS
authors.lastname: Jacob
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400 076, India.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Singh
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400 076, India.
authors.forename: Narasimham
authors.initials: N
authors.lastname: Ayyagari
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400 076, India.
authors.forename: Irishi N N
authors.initials: IN
authors.lastname: Namboothiri
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400 076, India.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Maji
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D003474:Curcumin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D066329:Protein Aggregates / Q000187:drug effects; D011485:Protein Binding; D013053:Spectrophotometry; D017550:Spectroscopy, Fourier Transform Infrared; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D066329:Protein Aggregates; D051844:alpha-Synuclein; D003474:Curcumin