title: ANS binding reveals common features of cytotoxic amyloid species.
abstract: Oligomeric assemblies formed from a variety of disease-associated peptides and proteins have been strongly associated with toxicity in many neurodegenerative conditions, such as Alzheimer's disease. The precise nature of the toxic agents, however, remains still to be established. We show that prefibrillar aggregates of E22G (arctic) variant of the Abeta(1-42) peptide bind strongly to 1-anilinonaphthalene 8-sulfonate and that changes in this property correlate significantly with changes in its cytotoxicity. Moreover, we show that this phenomenon is common to other amyloid systems, such as wild-type Abeta(1-42), the I59T variant of human lysozyme and an SH3 domain. These findings are consistent with a model in which the exposure of hydrophobic surfaces as a result of the aggregation of misfolded species is a crucial and common feature of these pathogenic species.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bolognesi
authors.forename: Janet R
authors.initials: JR
authors.lastname: Kumita
authors.forename: Teresa P
authors.initials: TP
authors.lastname: Barros
authors.forename: Elin K
authors.initials: EK
authors.lastname: Esbjorner
authors.forename: Leila M
authors.initials: LM
authors.lastname: Luheshi
authors.forename: Damian C
authors.initials: DC
authors.lastname: Crowther
authors.forename: Mark R
authors.initials: MR
authors.lastname: Wilson
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.forename: Giorgio
authors.initials: G
authors.lastname: Favrin
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Yerbury
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics; D000817:Anilino Naphthalenesulfonates; D002460:Cell Line; D005453:Fluorescence; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D000817:Anilino Naphthalenesulfonates; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C027132:1-anilino-8-naphthalenesulfonate; D009113:Muramidase