title: Cysteine inhibits the fibrillisation and cytotoxicity of amyloid-β 40 and 42: implications for the contribution of the thiophilic interaction.
abstract: Inhibitors of amyloid fibril formation have been at the centre of intense research efforts for the prevention of amyloidosis. Here, we hypothesise that a specific non-covalent interaction, the thiophilic interaction between the side chain of an aromatic residue in a polypeptide and a sulphur atom of the compound, effectively inhibits amyloid fibril formation. Fluorescence spectroscopy and transmission electron microscopy revealed that sulphur compounds, particularly Cys, inhibit the fibrillisation of amyloid-β 1-40 (Aβ40) and 1-42 (Aβ42). Interestingly, aggregates of Aβ40 and Aβ42 induced by Cys were less cytotoxic than those induced by catechin, which is the most typical inhibitor of amyloid fibril formation. Because the essential amino acid, Cys, is an abundant molecule in the blood and cytosol, our data provide a new basis for the prevention of amyloid-related diseases and the elucidation of the mechanism of these diseases.
authors.affiliation: Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan. shiraki@bk.tsukuba.ac.jp.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Takai
authors.forename: Ken
authors.initials: K
authors.lastname: Uda
authors.forename: Tomonori
authors.initials: T
authors.lastname: Yoshida
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Zako
authors.forename: Mizuo
authors.initials: M
authors.lastname: Maeda
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shiraki
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D002392:Catechin / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D003545:Cysteine / Q000737:chemistry* / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D011485:Protein Binding; D051381:Rats; D013455:Sulfur / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D013455:Sulfur; D002392:Catechin; D003545:Cysteine