Human pregnancy zone protein stabilizes misfolded proteins including preeclampsia- and Alzheimer’s-associated amyloid beta peptide

著者: Jordan H. Cater, Janet R. Kumita, Rafaa Zeineddine Abdallah, Guomao Zhao, Ana Bernardo-Gancedo, Amanda Henry, Wendy Winata, Mengna Chi, Brin F. S. Grenyer, Michelle L. Townsend, Marie Ranson, Catalin S. Buhimschi, D. Stephen Charnock‐Jones, Christopher M. Dobson, Mark R. Wilson, Irina A. Buhimschi, Amy R. Wyatt - Proceedings of the National Academy of Sciences, PNAS 2019 被引用: 92

M is enhanced by inducing its dissociation into PZP-like dimers. By immunohistochemistry analysis, PZP is found primarily in extravillous trophoblasts in the placenta. In severe preeclampsia, PZP-positive extravillous trophoblasts are adjacent to extracellular plaques containing Aβ, but PZP is not abundant within extracellular plaques. Our data support the conclusion that the up-regulation of PZP during pregnancy represents a major maternal adaptation that helps to maintain extracellular proteostasis during gestation in humans. We propose that overwhelming or disrupting the chaperone function of PZP could underlie the accumulation of misfolded proteins in vivo. Attempts to characterize extracellular proteostasis in pregnancy will potentially have broad-reaching significance for understanding disease-related protein misfolding.