Journal article

PrPSc Oligomerization Appears Dynamic, Quickly Engendering Inherent M1000 Acute Synaptotoxicity

Simote T Foliaki, Victoria Lewis, Abu MT Islam, Matteo Senesi, David Finkelstein, Laura J Ellett, Victoria A Lawson, Paul A Adlard, Blaine R Roberts, Steven J Collins

Biophysical Journal | CELL PRESS | Published : 2020

Abstract

Prion diseases are neurodegenerative disorders pathogenically linked to cellular prion protein (PrPC) misfolding into abnormal conformers (PrPSc), with PrPSc underpinning both transmission and synaptotoxicity. Although the biophysical features of PrPSc required to induce acute synaptic dysfunction remain incompletely defined, we recently reported that acutely synaptotoxic PrPSc appeared to be oligomeric. We herein provide further insights into the kinetic and requisite biophysical characteristics of acutely synaptotoxic ex vivo PrPSc derived from the brains of mice dying from M1000 prion disease. Pooled fractions of M1000 PrPSc located within the molecular weight range approximating monomeri..

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Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

S.J.C. is supported in part by a National Health and Medical Research Council Practitioner Fellowship (identification #APP1105784). S.T.F. was supported by a Creutzfeldt-Jakob disease Support Group Network (CJDSGN) Memorial Grant in memory of Dominic Battista.