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New Insights into Prion Structure and Toxicity

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1 New Insights into Prion Structure and Toxicity
David A. Harris, Heather L. True  Neuron  Volume 50, Issue 3, Pages (May 2006) DOI: /j.neuron Copyright © 2006 Elsevier Inc. Terms and Conditions

2 Figure 1 Models for the Cellular Toxicity of PrPSc
(A) Toxic gain-of-function mechanism. PrPSc (or PrPtoxic, a pathogenic intermediate) possesses a novel neurotoxic activity that is independent of the normal function of PrPC. (B) Loss-of-function mechanism. PrPC possesses a normal, physiological activity, in this case neuroprotection, that is lost upon conversion to PrPSc. (C) Subversion-of-function mechanism. The normal, neuroprotective activity of PrPC is subverted by binding to PrPSc (or PrPtoxic). Cross-hatching of the rectangle representing PrPC indicates a change in its signaling properties such that a neurotoxic rather than a neuroprotective signal is delivered. In the absence of the GPI anchor attaching PrPC to the membrane, no signal would be delivered and disease would not occur, as was observed in the study of Chesebro et al. (2005). Neuron  , DOI: ( /j.neuron ) Copyright © 2006 Elsevier Inc. Terms and Conditions

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