Rescue of Transgenic Alzheimer's Pathophysiology by Polymeric Cellular Prion Protein Antagonists.

ABSTRACT: Cellular prion protein (PrP^C) binds the scrapie conformation of PrP (PrP^Sc) and oligomeric β-amyloid peptide (Aβo) to mediate transmissible spongiform encephalopathy (TSE) and Alzheimer's disease (AD), respectively. We conducted cellular and biochemical screens for compounds blocking PrP^C interaction with Aβo. A polymeric degradant of an antibiotic targets Aβo binding sites on PrP^C with low nanomolar affinity and prevents Aβo-induced pathophysiology. We then identified a range of negatively charged polymers with specific PrP^C affinity in the low to sub-nanomolar range, from both biological (melanin) and synthetic (poly [4-styrenesulfonic acid-co-maleic acid], PSCMA) origin. Association of PSCMA with PrP^C prevents Aβo/PrP

SUBMITTER: Gunther EC 

PROVIDER: S-EPMC6358723 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature