Journal article

Glycosaminoglycan Sulphation Affects the Seeded Misfolding of a Mutant Prion Protein

Victoria A Lawson, Brooke Lumicisi, Jeremy Welton, Dorothy Machalek, Katrina Gouramanis, Helen M Klemm, James D Stewart, Colin L Masters, David E Hoke, Steven J Collins, Andrew F Hill

PLoS One | PUBLIC LIBRARY SCIENCE | Published : 2010

Abstract

BACKGROUND: The accumulation of protease resistant conformers of the prion protein (PrP(res)) is a key pathological feature of prion diseases. Polyanions, including RNA and glycosaminoglycans have been identified as factors that contribute to the propagation, transmission and pathogenesis of prion disease. Recent studies have suggested that the contribution of these cofactors to prion propagation may be species specific. METHODOLOGY/PRINCIPAL FINDING: In this study a cell-free assay was used to investigate the molecular basis of polyanion stimulated PrP(res) formation using brain tissue or cell line derived murine PrP. Enzymatic depletion of endogenous nucleic acids or heparan sulphate (HS) ..

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Grants

Awarded by National Health and Medical Research Council (NHMRC)


Funding Acknowledgements

This work was supported by National Health and Medical Research Council (NHMRC) Project Grant #400229 and The University of Melbourne Research Grant Scheme. VAL is the recipient of an NHMRC Howard Florey Fellowship and University of Melbourne CR Roper Fellowship. AFH is the recipient of an NHMRC RD Wright Career Development Award, and SJC is a recipient of an NHMRC Practitioner Fellowship #400183. JW is the recipient of the Mary Stewart Bursary from the Faculty of Medicine, University of Melbourne. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.