title: Attenuation of lysozyme amyloid cytotoxicity by SPION-mediated modulation of amyloid aggregation.
abstract: The formation and deposition of proteinaceous aggregates of amyloid fibrils characterize diverse degenerative diseases, such as Alzheimer's, Parkinson's, and systemic amyloidosis. The presence of these aggregates is associated with clinical manifestations, and various forms of amyloid aggregates have been identified to be cytotoxic. Although the exact mechanism of amyloid toxicity remains to be elucidated, prevention of amyloid fibril formation and aggregation forms a possible therapeutic approach. Nanomaterials possess the potential for such a strategy. Using hen egg white lysozyme (HEWL) as a prototypic amyloid-forming protein, we found a reduction in the aggregation rate of HEWL in the presence of super-paramagnetic iron oxide nanoparticles (SPIONs) with slowing of nucleation and amyloid fibril elongation. HEWL-amyloid had a predominantly fibrillar structure and was toxic to various cells. A significant attenuation of cytotoxicity was observed when cells were treated with SPION-interacted HEWL-amyloid. Ultra-structural differences were observed between the native and SPION-interacted HEWL-amyloids by SEM and TEM imaging. Our findings confirm that SPIONs perturb amyloid fibrillation, thereby reducing the cytotoxicity of amyloid.
authors.affiliation: UM-DAE Centre for Excellence in Basic Sciences, Vidyanagari, Santacruz (E), Mumbai 400098, India.
authors.forename: Aafreen
authors.initials: A
authors.lastname: Naik
authors.affiliation: University Department of Biotechnology, University of Mumbai, Vidyanagari, Santacruz (East), Mumbai 400098, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Kambli
authors.affiliation: UM-DAE Centre for Excellence in Basic Sciences, Vidyanagari, Santacruz (E), Mumbai 400098, India.
authors.forename: Mohanish
authors.initials: M
authors.lastname: Borana
authors.affiliation: UM-DAE Centre for Excellence in Basic Sciences, Vidyanagari, Santacruz (E), Mumbai 400098, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Mohanpuria
authors.affiliation: UM-DAE Centre for Excellence in Basic Sciences, Vidyanagari, Santacruz (E), Mumbai 400098, India.
authors.forename: Basir
authors.initials: B
authors.lastname: Ahmad
authors.affiliation: University Department of Biotechnology, University of Mumbai, Vidyanagari, Santacruz (East), Mumbai 400098, India.
authors.forename: Varsha
authors.initials: V
authors.lastname: Kelkar-Mane
authors.affiliation: UM-DAE Centre for Excellence in Basic Sciences, Vidyanagari, Santacruz (E), Mumbai 400098, India. Electronic address: brainwave.surf@gmail.com.
authors.forename: Uma
authors.initials: U
authors.lastname: Ladiwala
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D066329:Protein Aggregates
chemical_list: D000682:Amyloid; D058185:Magnetite Nanoparticles; D066329:Protein Aggregates; C421864:hen egg lysozyme; D009113:Muramidase
keywords: Aggregation kinetics; Amyloid; Cytotoxicity; SPIONs