title: Efficient Inhibition of Protein Aggregation, Disintegration of Aggregates, and Lowering of Cytotoxicity by Green Tea Polyphenol-Based Self-Assembled Polymer Nanoparticles.
abstract: Green tea polyphenol epigallocatechin-3-gallate (EGCG) is known for its antiamyloidogenic property, and it is observed that molecular EGCG binds with amyloid structure, redirects fibrillation kinetics, remodels mature fibril, and lowers the amyloid-derived toxicity. However, this unique property of EGCG is difficult to utilize because of their poor chemical stability and substandard bioavailability. Here we report a nanoparticle form of EGCG of 25 nm size (nano-EGCG) which is 10-100 times more efficient than molecular EGCG in inhibiting protein aggregation, disintegrating mature protein aggregates, and lowering amyloidogenic cytotoxicity. The most attractive advantage of nano-EGCG is that it efficiently protects neuronal cells from the toxic effect of extracellular amyloid beta or intracellular mutant huntingtin protein aggregates by preventing their aggregation. We found that the better performance of nano-EGCG is due to the combined effect of increased chemical stability of EGCG against degradation, stronger binding with protein aggregates, and efficient entry into the cell for interaction with aggregated protein structure. This result indicates that the nanoparticle form of antiamyloidogenic molecules can be more powerful in prevention and curing of protein aggregation derived diseases.
authors.affiliation: Centre for Advanced Materials, Indian Association for the Cultivation of Science , Kolkata 700032, India.
authors.forename: Koushik
authors.initials: K
authors.lastname: Debnath
authors.affiliation: Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre , Manesar, Gurgaon 122051, India.
authors.forename: Shashi
authors.initials: S
authors.lastname: Shekhar
authors.affiliation: Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre , Manesar, Gurgaon 122051, India.
authors.forename: Vipendra
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre , Manesar, Gurgaon 122051, India.
authors.forename: Nihar R
authors.initials: NR
authors.lastname: Jana
authors.affiliation: Centre for Advanced Materials, Indian Association for the Cultivation of Science , Kolkata 700032, India.
authors.forename: Nikhil R
authors.initials: NR
authors.lastname: Jana
keywords: EGCG; Huntington’s disease; amyloid; biopolymer; green tea polyphenol; nanoparticle