Prion acute synaptotoxicity is largely driven by protease-resistant PrPScspecies

ST Foliaki; V Lewis; DI Finkelstein; V Lawson; HA Coleman; M Senesi; AMT Islam; F Chen; S Sarros; B Roberts; PA Adlard; SJ Collins

Journal article

Prion acute synaptotoxicity is largely driven by protease-resistant PrPScspecies

ST Foliaki, V Lewis, DI Finkelstein, V Lawson, HA Coleman, M Senesi, AMT Islam, F Chen, S Sarros, B Roberts, PA Adlard, SJ Collins

Plos Pathogens | Published : 2018

DOI: 10.1371/journal.ppat.1007214

Download PDF

Abstract

Although misfolding of normal prion protein (PrPC) into abnormal conformers (PrPSc) is critical for prion disease pathogenesis our current understanding of the underlying molecular pathophysiology is rudimentary. Exploiting an electrophysiology paradigm, herein we report that at least modestly proteinase K (PK)-resistant PrPSc(PrPres) species are acutely synaptotoxic. Brief exposure to ex vivo PrPScfrom two mouse-adapted prion strains (M1000 and MU02) prepared as crude brain homogenates (cM1000 and cMU02) and cell lysates from chronically M1000-infected RK13 cells (MoRK13-Inf) caused significant impairment of hippocampal CA1 region long-term potentiation (LTP), with the LTP disruption approx..

View full abstract

University of Melbourne Researchers

Vicki Lewis Author

David Finkelstein Author

Vicki Lawson Author

Matteo Senesi Author

Related Projects (1)

TACKLING KEY EPIDEMIOLOGICAL AND BASIC SCIENTIFIC RESEARCH ISSUES IN PRION DISEASES.

Proposed Practitioner Fellowship research will simultaneously include epidemiological and basic scientific projects, emphasising human prion..

Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

SJC is supported in part by an NHMRC Pracititioner Fellowship (#APP1105784). BR is a NHMRC Dementia Leadership Fellow (#APP1138673) and receives partial support from the Cooperative Research Centre for Mental Health (#20100104). STF has received the following support: University of Melbourne MIR Scholarship (2014); MIFR Scholarship (2014); CJD Support Group Network (CJDSGN) Silva Coehlho Travel Grant (2016); Marek Gorcynski Top-up scholarship (2017); and Dominic Battista Memorial Grant (2018). VL has received CJDSGN Memorial grants: Stephen O'Hara, Jennifer Duckworth and others lost to CJD (2018); Sandra Kernahan, Stephen O'Hara, Catherine Heagerty, Grasso family, Victoria Larielle, Barbara Childerhouse, Marilyn Hart and Pamela Thomas (2016); and Ross Glasscock, Robert Craig, Carmelo Tripoli, Arthur Schinck and Arlene Hamilton (2015). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.