Small heat shock proteins inhibit in vitro A beta(1-42) amyloidogenesis.
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.
Kudva
Y C
YC
Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Hiddinga
H J
HJ
Butler
P C
PC
Mueske
C S
CS
Eberhardt
N L
NL
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
D000682:Amyloid; D016229:Amyloid beta-Peptides; D006360:Heat-Shock Proteins; D010446:Peptide Fragments