RESUMO
Amyloid-ß (Aß) peptides represent key players in the pathogenesis of Alzheimer's disease (AD), and mounting evidence indicates that soluble Aß oligomers mediate the toxicity. Prefoldin (PFD) is a molecular chaperone that prevents aggregation of misfolded proteins. Here we investigated the role of PFD in Aß aggregation. First, we demonstrated that PFD is expressed in mouse brain by Western blotting and immunohistochemistry and found that PFD is upregulated in AD model APP23 transgenic mice. Then we investigated the effect of recombinant human PFD (hPFD) on Aß(1-42) aggregation in vitro and found that hPFD inhibited Aß fibrillation and induced formation of soluble Aß oligomers. Interestingly, cell viability measurements using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that Aß oligomers formed by hPFD were 30-40% less toxic to cultured rat pheochromocytoma (PC12) cells or primary cortical neurons from embryonic C57BL/6CrSlc mice than previously reported Aß oligomers (formed by archaeal PFD) and Aß fibrils (p < 0.001). Thioflavin T measurements and immunoblotting indicated different structural properties for the different Aß oligomers. Our findings show a relation between cytotoxicity of Aß oligomers and structure and suggest a possible protective role of PFD in AD.