JÖRG TATZELT



ABERRANT PROTEIN FOLDING AND NEURODEGENERATION


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, yeast, neuronal cell culture and animal models to focus on three major topics:

  • Cellular mechanisms underlying the formation and toxic activity of aberrant protein conformers
  • Signaling pathways induced by neurotoxic conformers
  • Therapeutic strategies for neurodegenerative diseases

SELECTED PUBLICATIONS


link to PubMed




Linsenmeier et al. (2021) Ligands binding to the prion protein induce its proteolytic release with therapeutic potential in neurodegenerative proteinopathies Sci Adv. doi: 10.1126/sciadv.abj1826. Epub 2021 Nov 24.

Polido et al. (2021) Biological Functions of the Intrinsically Disordered N-Terminal Domain of the Prion Protein: A Possible Role of Liquid-Liquid Phase Separation Biomolecules doi: 10.3390/biom11081201.

Kamps et al. (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. J Biol Chem. doi: 10.1016/j.jbc.2021.100860. Online ahead of print.

Ahlers et al. (2021). The key role of solvent in condensation: Mapping hydration water in liquid-liquid phase-separated FUS. Biophys J, 120(7):1266-1275.

Jung et al. (2020). SecY-mediated quality control prevents the translocation of non-gated porins. Sci Rep, 10(1):16347.

van Well, Bader et al. (2019). A protein quality control pathway regulated by linear ubiquitination. EMBO J., 38(9): doi: 10.15252/embj.2018100730.
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Engelke et al. (2018). Dimerization of the cellular prion protein inhibits propagation of scrapie prions. J Biol Chem, 293(21): 8020-8031.

Gonsberg et al. (2017). The Sec61/SecY complex is inherently deficient in translocating intrinsically disordered proteins. J Biol Chem, 292(52): 21383-21396.

Wu et al. (2017). The N-terminus of the prion protein is a toxic effector regulated by the C-terminus. Elife, 6. doi: 10.7554/eLife.23473.

Woerner et al. (2016). Cytoplasmic protein aggregates interfere with nucleo-cytoplasmic transport of protein and RNA. Science, 351(6269): 173-176.

Resenberger et al. (2011). The cellular prion protein mediates neurotoxic signaling of ß-sheet-rich conformers independent of prion replication. EMBO J, 30: 2057-2070.