title: Disclosure of a fundamental clue for the elucidation of the myricetin mechanism of action as amyloid aggregation inhibitor by mass spectrometry.
abstract: Progression of Alzheimer's disease involves aggregation of amyloid-beta (Aβ) peptides, a complex process that involves the formation of several soluble intermediates and ends up with the deposition of ordered fibrillar architectures. The determination of the Aβ42 self-assembly species targeted by an inhibitor is a key step in the identification of new inhibitors endowed with a suitable profile. In this context, the subtle characterization of myricetin (Myr) mode of action at a molecular level was performed by using different MS techniques, which allowed the monitoring of the modifications induced by Myr on the first occurring Aβ42 self-assembly species. Results showed a persistent level of monomer and decreased formation of ordered Aβ42 aggregates in the presence of Myr, further, nano-LC-nano-ESI-QTOF, MALDI-TOF, and ESI-IT highlighted the formation of a new oxidized Aβ42 species, which is less prone to aggregation, in the presence of Myr. Coupling tryptic digestion and nano-LC-nano-ESI-QTOF also allowed the identification of Met(35)  as the specific site of oxidation along the Aβ aminoacid chain. Therefore, the detailed investigation by different MS techniques allowed better understanding of the molecular modification at the basis of the antiaggregating properties of Myr and highlighted its oxidizing action on the residue Met(35)  in Aβ monomers.
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Fiori
authors.forename: Marina
authors.initials: M
authors.lastname: Naldi
authors.forename: Manuela
authors.initials: M
authors.lastname: Bartolini
authors.forename: Vincenza
authors.initials: V
authors.lastname: Andrisano
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D002853:Chromatography, Liquid; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D014357:Trypsin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D005419:Flavonoids; D010446:Peptide Fragments; C040015:myricetin; D014357:Trypsin