TY - JOUR AU - Resenberger, Ulrike K AU - Winklhofer, Konstanze F AU - Tatzelt, Jörg TI - Neuroprotective and neurotoxic signaling by the prion protein. JO - Topics in current chemistry VL - 305 SN - 0340-1022 CY - Heidelberg PB - Springer M1 - DZNE-2020-02777 SN - 978-3-642-24066-9 (print) T2 - Topics in Current Chemistry SP - 101-119 PY - 2011 AB - Prion diseases in humans and animals are characterized by progressive neurodegeneration and the formation of infectious particles called prions. Both features are intimately linked to a conformational transition of the cellular prion protein (PrP(C)) into aberrantly folded conformers with neurotoxic and self-replicating activities. Interestingly, there is increasing evidence that the infectious and neurotoxic properties of PrP conformers are not necessarily coupled. Transgenic mouse models revealed that some PrP mutants interfere with neuronal function in the absence of infectious prions. Vice versa, propagation of prions can occur without causing neurotoxicity. Consequently, it appears plausible that two partially independent pathways exist, one pathway leading to the propagation of infectious prions and another one that mediates neurotoxic signaling. In this review we will summarize current knowledge of neurotoxic PrP conformers and discuss the role of PrP(C) as a mediator of both stress-protective and neurotoxic signaling cascades. KW - Animals KW - Humans KW - Mice KW - Models, Biological KW - Mutation KW - Neurodegenerative Diseases: metabolism KW - Neurons: metabolism KW - Neurons: pathology KW - Neurotoxicity Syndromes: metabolism KW - Prion Diseases: metabolism KW - Prion Diseases: pathology KW - Prions: metabolism KW - Protein Conformation KW - Protein Denaturation KW - Protein Folding KW - Protein Structure, Tertiary KW - Signal Transduction KW - Prions (NLM Chemicals) LB - PUB:(DE-HGF)3 ; PUB:(DE-HGF)16 C6 - pmid:21598098 DO - DOI:10.1007/128_2011_160 UR - https://pub.dzne.de/record/136455 ER -