title: Flavonoids and Their Glycosides as Anti-amyloidogenic Compounds: Aβ1-42 Interaction Studies to Gain New Insights into Their Potential for Alzheimer's Disease Prevention and Therapy.
abstract: Combining NMR spectroscopy, transmission electron microscopy, biochemical and in vitro toxicity assays, we characterized the effect of flavonoid glycosylation, a chemical modification found very frequently in nature, on their ability to recognize and bind Aβ1-42 oligomers, preventing their aggregation and their neurotoxicity. Our data allow the elucidation of their structure-activity relationships, showing that glycosylation has a modest impact on flavonoid affinity for Aβ oligomers but, at the same time, increases both solubility and chemical stability, thus promoting their beneficial properties against Alzheimer's disease (AD). As flavonoids and their glycosides are widely available in natural foods, our results provide important information for the evaluation of the role of a flavonoid-rich diet for the prevention of AD. In addition, the structural data collected can be exploited for the rational design of more potent Aβ oligomer inhibitors, useful for the development of new therapies against AD.
authors.affiliation: Department of Biotecnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, I-20126, Milan, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Guzzi
authors.affiliation: Department Biochemistry and Molecular Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Via Giuseppe La Masa, 19, 20156, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Colombo
authors.affiliation: Department Biochemistry and Molecular Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Via Giuseppe La Masa, 19, 20156, Milan, Italy.
authors.forename: Ada De
authors.initials: A
authors.lastname: Luigi
authors.affiliation: Department Biochemistry and Molecular Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Via Giuseppe La Masa, 19, 20156, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.affiliation: Department of Biotecnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, I-20126, Milan, Italy.|Milan Center of Neuroscience (NeuroMI), 20126, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nicotra
authors.affiliation: Department of Biotecnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, I-20126, Milan, Italy.|Milan Center of Neuroscience (NeuroMI), 20126, Milan, Italy.
authors.forename: Cristina
authors.identifier: http://orcid.org/0000-0002-3670-6262
authors.initials: C
authors.lastname: Airoldi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000592:standards; D015394:Molecular Structure; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000737:chemistry; D066329:Protein Aggregates / Q000187:drug effects; D012015:Reference Standards; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D005419:Flavonoids; D006027:Glycosides; D010446:Peptide Fragments; D066329:Protein Aggregates; C442220:amyloid beta-protein (2-42)
keywords: Aβ peptide ligands; NMR spectroscopy; anti-amyloidogenic compounds; flavonoid glycosylation; molecular recognition studies