title: Sugar-Terminated Nanoparticle Chaperones Are 102-105Times Better Than Molecular Sugars in Inhibiting Protein Aggregation and Reducing Amyloidogenic Cytotoxicity.
abstract: Sugar-based osmolyte molecules are known to stabilize proteins under stress, but usually they have poor chaperone performance in inhibiting protein aggregation. Here, we show that the nanoparticle form of sugars molecule can enhance their chaperone performance typically by 102-105times, compared to molecular sugar. Sugar-based plate-like nanoparticles of 20-40 nm hydrodynamic size have been synthesized by simple heating of acidic aqueous solution of glucose/sucrose/maltose/trehalose. These nanoparticles have excitation-dependent green/yellow/orange emission and surface chemistry identical to the respective sugar molecule. Fibrillation of lysozyme/insulin/amyloid beta in extracellular space, aggregation of mutant huntingtin protein inside model neuronal cell, and cytotoxic effect of fibrils are investigated in the presence of these sugar nanoparticles. We found that sugar nanoparticles are 102-105times efficient than respective sugar molecules in inhibiting protein fibrillation and preventing cytotoxicity arising of fibrils. We propose that better performance of the nanoparticle form is linked to its stronger binding with fibril structure and enhanced cell uptake. This result suggests that nanoparticle form of osmolyte can be an attractive option 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: Nibedita
authors.initials: N
authors.lastname: Pradhan
authors.affiliation: Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre , Manesar, Gurgaon-122051, India.
authors.forename: Shashi
authors.identifier: http://orcid.org/0000-0003-1077-407X
authors.initials: S
authors.lastname: Shekhar
authors.affiliation: Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre , Manesar, Gurgaon-122051, India.
authors.forename: Nihar R
authors.identifier: http://orcid.org/0000-0002-6549-4211
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.identifier: http://orcid.org/0000-0002-4595-6917
authors.initials: NR
authors.lastname: Jana
mesh_terms: D000682:Amyloid; D016229:Amyloid beta-Peptides; D018832:Molecular Chaperones; D053758:Nanoparticles; D000073893:Sugars
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D018832:Molecular Chaperones; D000073893:Sugars
keywords: Huntington’s disease; amyloid fibril; chaperone; nanoparticle; osmolyte; sugar