Biochemie Neurodegenerativer Erkrankungen
Institut für Biochemie und Pathobiochemie
Medizinische Fakultät
Ruhr-Universität Bochum
Universitätsstr. 150
44801 Bochum
Raum:
MA 2/145
Tel:
+49 (0)234 32-22429
Email:
joerg.tatzelt@ruhr-uni-bochum.de
Various approaches coming from neuropathology, genetics, animal modeling and biophysics have established a crucial role of protein misfolding in the pathogenic process of different neurodegenerative diseases, such as Alzheimer's disease, Parkinson’s disease, polyglutamine expansion diseases and prion diseases. However, there is an ongoing debate about the nature of the harmful proteinaceous species and how toxic conformers selectively damage neuronal populations.
The main aim of our biochemical research is to identify cellular factors and signaling cascades implicated in neuronal integrity and in the pathophysiological alterations leading to neurodegeneration. Our integrative research has a strong focus on the biochemical and cell biological analysis of cellular pathways, which are also of broad neurobiological interest. Specifically, we are employing in vitro, neuronal cell culture, and animal models to focus on four major topics:
• Cellular mechanisms underlying the formation and toxic activity of aberrant protein conformers
• Liquid-liquid phase separation and neurodegeneration
• Signaling pathways induced by neurotoxic conformers
• Therapeutic strategies for neurodegenerative diseases
Goel, S., Oliva, R., Jeganathan, S., Bader, V., Krause, L. J., Kriegler, S., Stender, I. D., Christine, C. W., Nakamura, K., Hoffmann, J.‑E., Winter, R., Tatzelt, J., & Winklhofer, K. F. (2023). Linear ubiquitination induces NEMO phase separation to activate NF-κB signaling. Life Science Alliance, 6(4). https://doi.org/10.26508/lsa.202201607
Kamps, J., Lin, Y., Oliva, R., Bader, V., Winter, R., Winklhofer, K. F. & Tatzelt, J. (2021). The N-terminal domain of the prion protein is required and sufficient for liquid–liquid phase separation: A crucial role of the Aβ-binding domain. Journal of Biological Chemistry, 297(1), 100860. https://doi.org/10.1016/j.jbc.2021.100860
van Well, E. M., Bader, V., Patra, M., Sánchez-Vicente, A., Meschede, J., Furthmann, N., Schnack, C., Blusch, A., Longworth, J., Petrasch-Parwez, E., Mori, K., Arzberger, T., Trümbach, D., Angersbach, L., Showkat, C., Sehr, D. A., Berlemann, L. A., Goldmann, P., Clement, A. M., . . . Tatzelt, J., Winklhofer, K. F. (2019). A protein quality control pathway regulated by linear ubiquitination. The EMBO Journal, 38(9). https://doi.org/10.15252/embj.2018100730
Woerner, A. C., Frottin, F., Hornburg, D., Feng, L. R., Meissner, F., Patra, M., Tatzelt, J., Mann, M., Winklhofer, K. F., Hartl, F. U., & Hipp, M. S. (2016). Cytoplasmic protein aggregates interfere with nucleocytoplasmic transport of protein and RNA. Science (New York, N.Y.), 351(6269), 173–176. https://doi.org/10.1126/science.aad2033
Pfeiffer, N. V., Dirndorfer, D., Lang, S., Resenberger, U. K., Restelli, L. M., Hemion, C., Miesbauer, M., Frank, S., Neutzner, A., Zimmermann, R., Winklhofer, K. F., & Tatzelt, J. (2013). Structural features within the nascent chain regulate alternative targeting of secretory proteins to mitochondria. The EMBO Journal, 32(7), 1036–1051. https://doi.org/10.1038/emboj.2013.46
Resenberger, U. K., Harmeier, A., Woerner, A. C., Goodman, J. L., Müller, V., Krishnan, R., Vabulas, R. M., Kretzschmar, H. A., Lindquist, S., Hartl, F. U., Multhaup, G., Winklhofer, K. F., & Tatzelt, J. (2011). The cellular prion protein mediates neurotoxic signalling of β-sheet-rich conformers independent of prion replication. The EMBO Journal, 30(10), 2057–2070. https://doi.org/10.1038/emboj.2011.86
Copyright © RDN 2024
Letzte Änderung: 28. Feb. 2024
