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Infectious and Pathogenic Forms of PrP

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Prions and Diseases

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Abstract

Prion diseases are transmitted by unconventional infectious agents (prions) generated by the conformational conversion of PrPC, a normal, cell-surface glycoprotein, into PrPSc, a misfolded isoform that propagates itself by a self-templating mechanism. Although PrPSc has commonly been considered the primary neurotoxic species in prion diseases, strong experimental evidence now challenges this dogma and suggests that alternative pathogenic forms of PrP may operate by altering the normal physiological function of PrPC. In the past 15 years, we and others have generated cellular and animal models for studying prion diseases that shed light on important aspects of PrP infectivity, aggregation, and toxicity. In this chapter, we review some of these results and discuss our current understanding of the molecular processes responsible for the formation of aberrant forms of PrP and their acquisition of infectious and toxic properties.

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Acknowledgments

This work was supported by grants from the National Institutes of Health (NS052526, NS040975, NS065244, and NS056376) to DAH and by a grant from the Creutzfeldt–Jakob Disease Foundation to EB and DAH.

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Authors and Affiliations

  1. Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA

    Emiliano Biasini Ph.D. & David A. Harris M.D.,Ph.D.

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  1. Emiliano Biasini Ph.D.
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  2. David A. Harris M.D.,Ph.D.
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Correspondence to David A. Harris M.D.,Ph.D. .

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Editors and Affiliations

  1. , Department of Pathology, Case Western Reserve University School o, 2085 Adelbert Road, Cleveland, 44106, Ohio, USA

    Wen-Quan Zou

  2. , Department of Neuropathology, Case Western Reserve University School o, 2085 Adelbert Road, Cleveland, 44106, Ohio, USA

    Pierluigi Gambetti

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Biasini, E., Harris, D.A. (2013). Infectious and Pathogenic Forms of PrP. In: Zou, WQ., Gambetti, P. (eds) Prions and Diseases. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5305-5_10

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