Interaction of prion protein with acetylcholinesterase: potential pathobiological implications in prion diseases.

ABSTRACT:

Introduction

The prion protein (PrP) binds to various molecular partners, but little is known about their potential impact on the pathogenesis of prion diseases

Results

Here, we show that PrP can interact in vitro with acetylcholinesterase (AChE), a key protein of the cholinergic system in neural and non-neural tissues. This heterologous association induced aggregation of monomeric PrP and modified the structural properties of PrP amyloid fibrils. Following its recruitment into PrP fibrils, AChE loses its enzymatic activity and enhances PrP-mediated cytotoxicity. Using several truncated PrP variants and specific tight-binding AChE inhibitors (AChEis), we then demonstrate that the PrP-AChE interaction requires two mutually exclusive sub-sites in PrP N-terminal domain and an a

SUBMITTER: Torrent J 

PROVIDER: S-EPMC4383067 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature