Cellular prion protein acts as mediator of amyloid beta uptake by caveolin-1 causing cellular dysfunctions in vitro and in vivo.

ABSTRACT:

Introduction

Cellular prion protein (PrP^C) was implicated in amyloid beta (Aβ)-induced toxicity in Alzheimer's disease (AD), but the precise molecular mechanisms involved in this process are unclear.

Methods

Double transgenic mice were generated by crossing Prnp knockout (KO) with 5xFAD mice, and light-sheet microscopy was used for whole brain tissue analyses. PrP^C-overexpressing cells were developed for in vitro studies, and microscopy was used to assess co-localization of proteins of interest. Surface-plasmon resonance (SPR) was used to investigate protein-binding characteristics.

Results

In vivo, PrP^C levels correlated with reduced lifespan and cognitive and motor function, and its ablation disconnected behavior deficits from Aβ lev

SUBMITTER: da Silva Correia A 

PROVIDER: S-EPMC11485400 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature