Early existence and biochemical evolution characterise acutely synaptotoxic PrPSc
Simote Totauhelotu Foliaki, Victoria Lewis, Abu Mohammed Taufiqual Islam, Laura Jane Ellett, Matteo Senesi, David Isaac Finkelstein, Blaine Roberts, Victoria A Lawson, Paul Anthony Adlard, Steven John Collins
PLOS PATHOGENS | PUBLIC LIBRARY SCIENCE | Published : 2019
Although considerable evidence supports that misfolded prion protein (PrPSc) is the principal component of "prions", underpinning both transmissibility and neurotoxicity, clear consensus around a number of fundamental aspects of pathogenesis has not been achieved, including the time of appearance of neurotoxic species during disease evolution. Utilizing a recently reported electrophysiology paradigm, we assessed the acute synaptotoxicity of ex vivo PrPSc prepared as crude homogenates from brains of M1000 infected wild-type mice (cM1000) harvested at time-points representing 30%, 50%, 70% and 100% of the terminal stage of disease (TSD). Acute synaptotoxicity was assessed by measuring the capa..View full abstract
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Awarded by Cooperative Research Centre for Mental Health
SJC is supported in part by an NHMRC Practitioner Fellowship (#APP1105784). BR is a NHMRC Dementia Leadership Fellow (#APP11 38673) and receives partial support from the Cooperative Research Centre for Mental Health (#20100104). SF has received a University of Melbourne MIR Scholarship (2014), a MIFR Scholarship (2014), a CJD Support Group Network (CJDSGN) Silva Coehlho Travel Grant (2016), a 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). These indirect funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.