Prion infections and anti-PrP antibodies trigger converging neurotoxic pathways

Herrmann, Uli S; Sonati, Tiziana; Falsig, Jeppe; Reimann, Regina R; Dametto, Paolo; O'Connor, Tracy; Li, Bei; Lau, Agnes; Hornemann, Simone; Sorce, Silvia; Wagner, Uli; Sanoudou, Despina; Aguzzi, Adriano

doi:10.1371/journal.ppat.1004662

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Herrmann, U. S., Sonati, T., Falsig, J., Reimann, R. R., Dametto, P., O’Connor, T., Li, B., Lau, A., Hornemann, S., Sorce, S., Wagner, U., Sanoudou, D., & Aguzzi, A. (2015). Prion infections and anti-PrP antibodies trigger converging neurotoxic pathways. PLoS Pathogens, 11(2), e1004662. https://doi.org/10.1371/journal.ppat.1004662

Abstract

Prions induce lethal neurodegeneration and consist of PrPSc, an aggregated conformer of the cellular prion protein PrPC. Antibody-derived ligands to the globular domain of PrPC (collectively termed GDL) are also neurotoxic. Here we show that GDL and prion infections activate the same pathways. Firstly, both GDL and prion infection of cerebellar organotypic cultured slices (COCS) induced the production of reactive oxygen species (ROS). Accordingly, ROS scavenging, which counteracts GDL toxicity in vitro and in vivo, prolonged the lifes