Understanding curcumin-induced modulation of protein aggregation.
Curcumin, a diarylheptanoid compound, found in spice turmeric is known to alter the aggregation of proteins and reduce the toxicity of the aggregates. This review looks at the molecular basis of modulating protein aggregation and toxicity of the aggregates. Foremost, we identify the interaction of curcumin and its derivatives with proteins/peptides and the effect of their interaction on the conformational stability and unfolding/folding pathway(s). The unfolding/folding processes generate partially folded/unfolded intermediate, which serve as aggregation precursor state. Secondly, we discuss the effect of curcumin binding on the kinetics parameters of the aggregation process, which give information about the mechanism of the aggregation inhibition. We describe, in addition, that curcumin can accelerate/promote fibril formation by binding to oligomeric intermediate(s) accumulated in the aggregation pathway. Finally, we discuss the correlation of curcumin-induced monomeric and/or oligomeric precursor states with aggregate structure and toxicity. On the basis of these discussions, we propose a model describing curcumin-induced inhibition/promotion of formation of amyloid-like fibrils.
Biophysical Chemistry & Structural Biology Laboratory, UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Vidyanagari Campus, Mumbai 400098, India. Electronic address: basir.ahmad@cbs.ac.in.
Basir
B
Ahmad
Biophysical Chemistry & Structural Biology Laboratory, UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Vidyanagari Campus, Mumbai 400098, India; EaStCHEM School of Chemistry, The University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JJ, United Kingdom.
Mohanish S
MS
Borana
Biophysical Chemistry & Structural Biology Laboratory, UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Vidyanagari Campus, Mumbai 400098, India.
Ankur P
AP
Chaudhary
D000682:Amyloid / Q000737:chemistry; D000818:Animals; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000633:toxicity; D066329:Protein Aggregates; D011506:Proteins / Q000737:chemistry* / Q000633:toxicity
D000682:Amyloid; D010455:Peptides; D066329:Protein Aggregates; D011506:Proteins; D003474:Curcumin
Aggregation inhibition; Aggregation modulation; Amyloidosis; Curcumin; Neurodegeneration