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|Title:||Effect of curcumin analogs on alpha-synuclein aggregation and cytotoxicity|
|Keywords:||Chemopreventive Agent Curcumin|
Amyloid Fibril Formation
|Publisher:||NATURE PUBLISHING GROUP|
|Abstract:||Alpha-synuclein (alpha-Syn) aggregation into oligomers and fibrils is associated with dopaminergic neuron loss occurring in Parkinson's disease (PD) pathogenesis. Compounds that modulate alpha-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 alpha-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 alpha-Syn aggregation to produce morphologically different amyloid fibrils in vitro. Furthermore, these curcumin analogs showed differential binding with the preformed alpha-Syn aggregates. The present data suggest the potential role of curcumin analogs in modulating alpha-Syn aggregation.|
|Appears in Collections:||Article|
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