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10 results on '"Frontzek, Karl'

1. A model of human neural networks reveals NPTX2 pathology in ALS and FTLD

Author

Hruska-Plochan, Marian, primary, Wiersma, Vera I., additional, Betz, Katharina M., additional, Mallona, Izaskun, additional, Ronchi, Silvia, additional, Maniecka, Zuzanna, additional, Hock, Eva-Maria, additional, Tantardini, Elena, additional, Laferriere, Florent, additional, Sahadevan, Sonu, additional, Hoop, Vanessa, additional, Delvendahl, Igor, additional, Pérez-Berlanga, Manuela, additional, Gatta, Beatrice, additional, Panatta, Martina, additional, van der Bourg, Alexander, additional, Bohaciakova, Dasa, additional, Sharma, Puneet, additional, De Vos, Laura, additional, Frontzek, Karl, additional, Aguzzi, Adriano, additional, Lashley, Tammaryn, additional, Robinson, Mark D., additional, Karayannis, Theofanis, additional, Mueller, Martin, additional, Hierlemann, Andreas, additional, and Polymenidou, Magdalini, additional

Published
2024
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2. A conformational switch controlling the toxicity of the prion protein

Author

Simon Jurt, Mattia Pedotti, Marika Marino, Luca Varani, Anna Henzi, Georg Meisl, Seden Bedir, Tuomas P. J. Knowles, Rohanah Hussain, Asvin K. K. Lakkaraju, Marco Losa, Federica Mazzola, Karl Frontzek, Marco Bardelli, Oliver Zerbe, Petra Schwarz, Giuliano Siligardi, Assunta Senatore, Adriano Aguzzi, Regina Reimann, Luca Simonelli, Simone Hornemann, Caihong Zhu, Matthew Holt, Frontzek, Karl [0000-0002-0945-8857], Bedir, Seden [0000-0002-8509-1268], Marino, Marika [0000-0001-6773-6176], Hussain, Rohanah [0000-0001-6207-6631], Meisl, Georg [0000-0002-6562-7715], Zerbe, Oliver [0000-0003-0475-438X], Losa, Marco [0000-0003-3428-418X], Knowles, Tuomas [0000-0002-7879-0140], Hornemann, Simone [0000-0002-2674-9891], Holt, Matthew G [0000-0002-8958-4027], Varani, Luca [0000-0002-0963-0987], Aguzzi, Adriano [0000-0002-0344-6708], Apollo - University of Cambridge Repository, University of Zurich, Varani, Luca, and Aguzzi, Adriano

Subjects
PRP, animal diseases, Mutant, RESISTANT, Ligands, 14, 13/1, Mice, 1315 Structural Biology, Structural Biology, Cerebellum, 540 Chemistry, 14/19, biology, Chemistry, Neurodegeneration, article, Cell biology, 631/45/460, Toxicity, Antibody, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, 101, Prions, Biophysics, 10208 Institute of Neuropathology, 101/6, 610 Medicine & health, Antibodies, Prion Proteins, 38, 82/80, Prion infection, 1312 Molecular Biology, medicine, Animals, PrPC Proteins, Prion protein, Molecular Biology, Science & Technology, 82, Neurotoxicity, Cell Biology, medicine.disease, NMR, nervous system diseases, MICE, 631/535/1267, REPLICATION, ANTIBODIES, 13/51, biology.protein, 570 Life sciences, Neurological impairment
Abstract

Funder: Ono PharmaceuticalsTheodo Ida Herzog-Egli Stiftung, Funder: Stavros Niarchos Foundation (SNF); doi: https://doi.org/10.13039/501100004343, Funder: RCUK | Biotechnology and Biological Sciences Research Council (BBSRC); doi: https://doi.org/10.13039/501100000268, Funder: EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council); doi: https://doi.org/10.13039/100010663, Funder: Frances and Augustus Newman Foundation; doi: https://doi.org/10.13039/100007898, Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: “Ideas” Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): H2020-WIDESPREAD-2018-2020-6; NCBio; 951923, Funder: FWO (Grant 1513616N), Funder: Lions Club Monteceneri, Funder: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation); doi: https://doi.org/10.13039/501100001711, Funder: Gelu Foundation, Swiss Initiative in Systems Biology, SystemsX.ch (PrionX, SynucleiX), Prion infections cause conformational changes of the cellular prion protein (PrPC) and lead to progressive neurological impairment. Here we show that toxic, prion-mimetic ligands induce an intramolecular R208-H140 hydrogen bond ('H-latch'), altering the flexibility of the α2-α3 and β2-α2 loops of PrPC. Expression of a PrP2Cys mutant mimicking the H-latch was constitutively toxic, whereas a PrPR207A mutant unable to form the H-latch conferred resistance to prion infection. High-affinity ligands that prevented H-latch induction repressed prion-related neurodegeneration in organotypic cerebellar cultures. We then selected phage-displayed ligands binding wild-type PrPC, but not PrP2Cys. These binders depopulated H-latched conformers and conferred protection against prion toxicity. Finally, brain-specific expression of an antibody rationally designed to prevent H-latch formation prolonged the life of prion-infected mice despite unhampered prion propagation, confirming that the H-latch is an important reporter of prion neurotoxicity.

Published
2022
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3. A conformational switch controlling the toxicity of the prion protein

Author

Frontzek, Karl, primary, Bardelli, Marco, additional, Senatore, Assunta, additional, Henzi, Anna, additional, Reimann, Regina R., additional, Bedir, Seden, additional, Marino, Marika, additional, Hussain, Rohanah, additional, Jurt, Simon, additional, Meisl, Georg, additional, Pedotti, Mattia, additional, Mazzola, Federica, additional, Siligardi, Giuliano, additional, Zerbe, Oliver, additional, Losa, Marco, additional, Knowles, Tuomas, additional, Lakkaraju, Asvin, additional, Zhu, Caihong, additional, Schwarz, Petra, additional, Hornemann, Simone, additional, Holt, Matthew G., additional, Simonelli, Luca, additional, Varani, Luca, additional, and Aguzzi, Adriano, additional

Published
2022
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6. Protective anti‐prion antibodies in human immunoglobulin repertoires

Author

Senatore, Assunta, primary, Frontzek, Karl, additional, Emmenegger, Marc, additional, Chincisan, Andra, additional, Losa, Marco, additional, Reimann, Regina, additional, Horny, Geraldine, additional, Guo, Jingjing, additional, Fels, Sylvie, additional, Sorce, Silvia, additional, Zhu, Caihong, additional, George, Nathalie, additional, Ewert, Stefan, additional, Pietzonka, Thomas, additional, Hornemann, Simone, additional, and Aguzzi, Adriano, additional

Published
2020
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7. Intravascular large B‑cell lymphoma

Author

Manfred Kessler, Elisabeth J. Rushing, Daniela Weiler, Jeanne Godau, Karl Frontzek, Silvia Hofer, and Stefan Aebi

Subjects
Pathology, medicine.medical_specialty, Chemotherapy, Intravascular large B-cell lymphoma, business.industry, medicine.medical_treatment, Myelitis, Hematology, Disease, medicine.disease, Lymphoma, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Oncology, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, Aphasia, medicine, Dementia, Radiology, medicine.symptom, business, Stroke
Abstract

Intravascular lymphoma (IVL), a rare, extranodal form of non-Hodgkin lymphoma (NHL), can cause infarcts by occluding small arteries of the brain. Owing to its heterogeneous clinical manifestations and unfavorable prognosis, the diagnosis is often made postmortem. Patients can present with a range of motor or sensory deficits, rapid cognitive impairment, aphasia or signs of myelitis, often with nonspecific radiographic findings.Timely recognition of a treatable disease is essential to prevent permanent neurocognitive defects. We present a case who could be treated successfully with chemotherapy.

Published
2016
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8. Intravascular large B‑cell lymphoma

Author

Hofer, Silvia, primary, Kessler, Manfred, additional, Godau, Jeanne, additional, Weiler, Daniela, additional, Frontzek, Karl, additional, Rushing, Elisabeth Jane, additional, and Aebi, Stefan, additional

Published
2016
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