Journal
BRAIN RESEARCH
Volume 1089, Issue -, Pages 67-78Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2006.03.058
Keywords
small heat shock protein; Alzheimer's disease; cerebrovascular amyloid; fibrillization; amyloid-beta protein
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Small heat shock proteins Hsp20 and HspB2/B3 co-localize with A beta deposition in senile plaques and cerebral amyloid angiopathy in Alzheimer's disease brains, respectively. It was the aim of our study to investigate if these and other sHsps bind to wild-type A beta(1-42) or the more toxic A beta(1-40) carrying the 'Dutch' mutation (22Glu-Gln) (D-A beta(1-40)), affect A beta aggregation and thereby influence A beta cytotoxicity. Binding affinity between sHsps and A beta was investigated by surface plasmon resonance. A beta aggregation was studied by using circular dichroism spectroscopy and electron microscopy. Furthermore, we used cultured cerebrovascular cells to investigate the effects of sHsps on A beta-mediated cytotoxicity. Hsp20, Hsp27 and alpha B-crystallin, but not HspB2/B3, bound to A beta (both D-A alpha(1-40) and A beta(1-42)) and reduced or completely inhibited aggregation of D-A beta(1-40) into mature fibrils but did not affect A beta(1-42) aggregation. Furthermore, these sHsps were effective inhibitors of the cerebrovascular toxicity of A beta (both D-A beta(1-40) and A beta(1-42)) in vitro. Binding affinity of the sHsps to D-A beta(1-40) correlated to the degree of inhibition of A beta-mediated cytotoxicity and the potential to reduce A beta beta-sheet and fibril formation. With A beta(1-42), a similar correlation between binding affinity and cytotoxicity was observed, but not with its aggregation state. In conclusion, sHsps may regulate A beta aggregation and serve as antagonists of the biological action of A beta but the extent of their interaction depends on the type of sHsp and A beta peptide. (c) 2006 Elsevier B.V. All rights reserved.
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