title: Natural compounds against neurodegenerative diseases: molecular characterization of the interaction of catechins from green tea with Aβ1-42, PrP106-126, and ataxin-3 oligomers.
abstract: By combining NMR spectroscopy, transmission electron microscopy, and circular dichroism we have identified the structural determinants involved in the interaction of green tea catechins with Aβ1-42, PrP106-126, and ataxin-3 oligomers. The data allow the elucidation of their mechanism of action, showing that the flavan-3-ol unit of catechins is essential for interaction. At the same time, the gallate moiety, when present, seems to increase the affinity for the target proteins. These results provide important information for the rational design of new compounds with anti-amyloidogenic activity and/or molecular tools for the specific targeting of amyloid aggregates in vivo.
authors.affiliation: Department of Biotechnology and Biosciences University of Milano-Bicocca, P.zza della Scienza, 2, 20126, Milano (Italy), Fax: (+39) 02-6448-3565.
authors.forename: Erika
authors.initials: E
authors.lastname: Sironi
authors.forename: Laura
authors.initials: L
authors.lastname: Colombo
authors.forename: Angela
authors.initials: A
authors.lastname: Lompo
authors.forename: Massimo
authors.initials: M
authors.lastname: Messa
authors.forename: Marcella
authors.initials: M
authors.lastname: Bonanomi
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Regonesi
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.forename: Cristina
authors.initials: C
authors.lastname: Airoldi
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000067699:Ataxin-3; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000517:prevention & control*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000517:prevention & control*; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D013662:Tea / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D001688:Biological Products; D005419:Flavonoids; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011328:Prions; D012097:Repressor Proteins; D013662:Tea; C075222:amyloid beta-protein (1-42); C082632:prion protein (106-126); C404987:flavan-3-ol; D002392:Catechin; C092341:ATXN3 protein, human; D000067699:Ataxin-3
keywords: NMR spectroscopy; amyloid peptides; circular dichroism; molecular recognition; structure-activity relationship