科研之友
微信
新浪微博
Facebook
分享链接
摘要
The prion protein (PrP) is best known for its association with prion diseases. However, a controversial new role for PrP in Alzheimer disease (AD) has recently emerged. In vitro studies and mouse models of AD suggest that PrP may be involved in AD pathogenesis through a highly specific interaction with amyloid-beta (A beta 42) oligomers. Immobilized recombinant human PrP (huPrP) also exhibited high affinity and specificity for A beta 42 oligomers. Here we report the novel finding that aggregated forms of huPrP and A beta 42 are co-purified from AD brain extracts. Moreover, an anti-PrP antibody and an agent that specifically binds to insoluble PrP (iPrP) co-precipitate insoluble A beta from human AD brain. Finally, using peptide membrane arrays of 99 13-mer peptides that span the entire sequence of mature huPrP, two distinct types of A beta binding sites on huPrP are identified in vitro. One specifically binds to A beta 42 and the other binds to both A beta 42 and A beta 40. Notably, A beta 42-specific binding sites are localized predominantly in the octapeptide repeat region, whereas sites that bind both A beta 40 and A beta 42 are mainly in the extreme N-terminal or C-terminal domains of PrP. Our study suggests that iPrP is the major PrP species that interacts with insoluble A beta 42 in vivo. Although this work indicated the interaction of A beta 42 with huPrP in the AD brain, the pathophysiological relevance of the iPrP/A beta 42 interaction remains to be established.
- 出版日期2011-4-29
