Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 May 7;11(5):e1004745.
doi: 10.1371/journal.ppat.1004745. eCollection 2015 May.

The elusive role of the prion protein and the mechanism of toxicity in prion disease

Roberto Chiesa  1
Affiliations
Review

The elusive role of the prion protein and the mechanism of toxicity in prion disease

Roberto Chiesa. PLoS Pathog. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The author has declared that no competing interests exist.

Figures

Fig 1
Fig 1. Theoretical model for how cell surface PrPC misfolding could result in neurotoxicity.
(A) PrPC consists of a flexible N terminus (mauve) and a globular C-terminal domain (green) attached to the plasma membrane (PM) by a GPI anchor (black line). PrPC associates with NMDARs, attenuating their activity [5]. (B–C) Interaction with extracellular PrPSc causes the N terminus of PrPC to undergo a structural rearrangement. This leads to aberrant interaction of PrPC with NMDARs and their hyperactivation (B) and/or abnormal insertion of the PrPC N terminus into the lipid bilayer with generation of a toxic pore (C). In addition to NMDARs, PrPC misfolding at the cell surface may corrupt the activity of other PrPC-interacting ion channels or signaling complexes.
Fig 2
Fig 2. A role for intracellular PrPC retention in neuronal dysfunction.
(A) PrPC on the plasma membrane (PM) influences the activity of neurotransmitter receptors, ion channels, and signaling complexes with which it interacts. (B) Owing to retention in transport organelles (ER/Golgi), misfolded/aggregated PrPC sequesters the interacting protein in intracellular compartments, leading to loss of normal function on the cell membrane [6]. Intracellular retention might also cause the complex to function abnormally and generate a toxic signal.
See this image and copyright information in PMC

References

    1. Malaga-Trillo E, Solis GP, Schrock Y, Geiss C, Luncz L, et al. (2009) Regulation of embryonic cell adhesion by the prion protein. PLoS Biol 7: e55 10.1371/journal.pbio.1000055 - DOI - PMC - PubMed
    1. Chiesa R, Harris DA (2009) Fishing for prion protein function. PLoS Biol 7: e75 10.1371/journal.pbio.1000075 - DOI - PMC - PubMed
    1. Steele AD, Lindquist S, Aguzzi A (2007) The prion protein knockout mouse: a phenotype under challenge. Prion 1: 83–93. - PMC - PubMed
    1. Linden R, Martins VR, Prado MA, Cammarota M, Izquierdo I, et al. (2008) Physiology of the prion protein. Physiol Rev 88: 673–728. 10.1152/physrev.00007.2007 - DOI - PubMed
    1. Khosravani H, Zhang Y, Tsutsui S, Hameed S, Altier C, et al. (2008) Prion protein attenuates excitotoxicity by inhibiting NMDA receptors. J Cell Biol 181: 551–565. 10.1083/jcb.200711002 - DOI - PMC - PubMed

Publication types

LinkOut - more resources