Medicine and Health Sciences Commons^™

The Prion Protein Ligand, Stress-Inducible Phosphoprotein 1, Regulates Amyloid-Beta Oligomer Toxicity, Valeriy G. Ostapchenko, Flavio H. Beraldo, Amro H. Mohammad, Yu-Feng Xie, Pedro H. F. Hirata, Ana C. Magalhaes, Guillaume Lamour, Hongbin Li, Andrzej Maciejewski, Jillian C. Belrose, Bianca L. Teixeira, Margaret Fahnestock, Sergio T. Ferreira, Neil R. Cashman, Glaucia N. M. Hajj, Michael F. Jackson, Wing-Yiu Choy, John F. Macdonald, Vilma R. Martins, Vania F. Prado, Marco A. M. Prado

Anatomy and Cell Biology Publications

In Alzheimer's disease (AD), soluble amyloid-beta oligomers (A beta Os) trigger neurotoxic signaling, at least partially, via the cellular prion protein (PrPC). However, it is unknown whether other ligands of PrPC can regulate this potentially toxic interaction. Stress-inducible phosphoprotein 1 (STI1), an Hsp90 cochaperone secreted by astrocytes, binds to PrPC in the vicinity of the A beta O binding site to protect neurons against toxic stimuli. Here, we investigated a potential role of STI1 in A beta O toxicity. We confirmed the specific binding of A beta Os and STI1 to the PrP and showed that STI1 efficiently inhibited A …