title: Small heat shock proteins inhibit in vitro A beta(1-42) amyloidogenesis.
abstract: We demonstrate that small heat shock proteins (sHsp) inhibit in vitro amyloid formation by the Alzheimer's A beta(1-42) polypeptide as detected by a thioflavine T fluorescence assay and electron microscopy. Human sHsp27 (0.50-3.0 microM) inhibited amyloid formation from 20 microM A beta(1-42) by 23-75%, in 24 h. In contrast, treatment of pre-formed amyloid with 0.5-3.0 microM sHsp27 only reduced the fluorescence signal by 6-36%. The data suggest that ordered fibril formation may represent a form of off-pathway aggregation that can be prevented by chaperone action. The data raise the possibility that age-related changes in chaperone function could contribute toward the pathogenesis of Alzheimer's and other amyloid-associated diseases.
authors.affiliation: Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Y C
authors.initials: YC
authors.lastname: Kudva
authors.forename: H J
authors.initials: HJ
authors.lastname: Hiddinga
authors.forename: P C
authors.initials: PC
authors.lastname: Butler
authors.forename: C S
authors.initials: CS
authors.lastname: Mueske
authors.forename: N L
authors.initials: NL
authors.lastname: Eberhardt
mesh_terms: D000682:Amyloid / Q000096:biosynthesis; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D006360:Heat-Shock Proteins; D010446:Peptide Fragments