title: Nanomedicine: action of metal nanoparticles on neuronal nitric oxide synthase-fluorimetric analysis on the mechanism for fibrillogenesis.
abstract: The incubation of neuronal nitric oxide synthase with the five amyloid peptide fragments [Aβ17-21; Aβ25-29; Aβ29-33; Aβ33-37; Aβ25-37] catalyzed the formation of fibrils. The role of neuronal isomer (nNOS) involved the entrapment of free monomers and seed aggregates to initiate the events of nucleation and elongation, critical for the formation of fibrils. It was evident that the hydrophobic nature of Aβ17-21, the three glycine zipper peptides [Aβ25-29; Aβ29-33; Aβ33-37] and Aβ25-37 was a trigger in the formation of fibrils and was a force critical in the association of the peptides with the enzyme. Gold and silver nanoparticles (average 4.0 nm) inhibited fibril formation when added to the induced fibrils from nNOS-Aβ incubation. The addition of nNOS and/or Aβ to co-incubated solutions of nanoparticle-Aβ or nanoparticle-nNOS respectively did not prevent fibril formation but reversed it. Three mechanisms for this reversal were proposed: (1) depletion of free Aβ monomer in solution and blocking potential aggregation sites on the nNOS molecule due to large surface area of the nanoparticle (2) hydrophobic interaction between the Aβ peptide and nanoparticle (3) disruption of binary adducts between Aβ-peptides and nNOS by nanoparticles.
authors.affiliation: Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, P.O. Box 94, Grahamstown, 6140, South Africa.
authors.forename: E R
authors.initials: ER
authors.lastname: Padayachee
authors.forename: A
authors.initials: A
authors.lastname: Arowolo
authors.forename: C G
authors.initials: CG
authors.lastname: Whiteley
mesh_terms: D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D005470:Fluorometry; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D050997:Nanomedicine; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D052248:Nitric Oxide Synthase Type I