Prof. Dr. Jörg Tatzelt

Gruppenleiter
Prof. Dr. Tatzelt ist am Adolf-Butenandt-Institut der LMU

Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
Schillerstraße 44
80336 München

joerg.tatzelt(at)dzne.de
+49 (0) 89 / 2180-75442
+49 (0) 89 / 2180-75415

Weitere Informationen

Gruppenmitglieder	Curriculum Vitae
Homepage Kooperationspartner

Forschungsschwerpunkte

Proteinmissfaltung und Neurodegeneration
Der neuronale Zelltod hängt bei verschiedenen neurodegenerativen Erkrankungen, wie der Alzheimer-Erkrankung, der Parkinson-Erkrankung, den Polyglutamin-Erkrankungen oder den Prion-Erkrankungen, kausal mit der Missfaltung von Proteinen zusammen. Unsere Forschung geht der Frage nach, wie es zur Bildung toxischer Proteinkonformere kommt und wie diese neuronalen Zelltod induzieren. Desweiteren untersuchen wir, welche physiologische Funktion die von der Missfaltung betroffenen Proteine bei der Homöostase neuronaler Zellen haben. Hierbei stehen vor allem Signaltransduktionskaskaden im Vordergrund, die für die neuronale Integrität und Funktionalität von Bedeutung sind.

Zum Einsatz kommen in vitro, Zellkultur- und transgene Tiermodelle, um folgende Themen zu bearbeiten:

Zelluläre Mechanismen, die der Bildung und toxischen Aktivität aberranter Protein-Konformere zugrunde liegen

Signalwege die durch neurotoxische Konformere induziert werden

Therapeutische Strategien für neurodegenerative Erkrankungen

Publikationen

Cellular prion protein mediates toxic signaling of amyloid Beta.

Resenberger UK, Winklhofer KF, Tatzelt J. Neurodegener Dis. 2012;10(1-4):298-300. Epub 2011 Dec 9.

Neuroprotective and Neurotoxic Signaling by the Prion Protein.

UK Resenberger, KF Winklhofer, J. Tatzelt, Top Curr Chem. 2011 May 20. [Epub ahead of print]

The cellular prion protein mediates neurotoxic signalling of β-sheet-rich conformers independent of prion replication.

UK Resenberger, A. Harmeier, AC Woerner, JL Goodman, V. Müller, R. Krishnan, RM Vabulas, HA Kretzschmar, S. Lindquist, FU Hartl, G. Multhaup, KF Winklhofer, J. Tatzelt, EMBO J. 2011 May 18;30(10):2057-70. Epub 2011 Mar 25.

Conserved stress-protective activity between prion protein and Shadoo.

V. Sakthivelu, RP Seidel, KF Winklhofer, J. Tatzelt, J Biol Chem. 2011 Mar 18;286(11):8901-8. Epub 2011 Jan 21.

Conditional modulation of membrane protein expression in cultured cells mediated by prion protein recognition of short phosphorothioate oligonucleotides.

Karpuj, M.V., Gelibter-Niv, S., Tiran, A., Rambold, A., Tatzelt, J.*, Nunziante, M.* and Schatzl, H.M.* (2011). J Biol Chem, 286, 6911-6917, Epub 2010 Dec 14.
*contributed equally

Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress.

Bouman, L., Schlierf, A., Lutz, A.K., Shan, J., Deinlein , A., Kast, J., Galehdar, Z., Palmisano, V., Patenge, N., Berg, D., Gasser, T., Augustin, R., Trümbach, D., Irrcher, I., Park, D., Wurst, W., Kilberg, M.S., Tatzelt, J. and Winklhofer, K.F. (2011), Cell Death Differ, 18, 769-782, Epub 2010 Nov 26.

Parkinson's disease-associated genes and mitochondrial integrity

AK Lutz, A. Pilsl, L. Bouman, J. Tatzelt, KF Winklhofer, BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, Volume 1797, Supplement 1, July 2010, Page 75

Protein Immobilization on Liposomes and Lipid Coated Nanoparticles by Protein Trans Splicing.

Chu, N.K., Olschewski, D., Seidel R., Winklhofer K.F., Tatzelt J., Engelhard M. and Becker C.F.W. (2010), J Pept Sci, 16, 582-588.

Parkin is protective against proteotoxic stress in a transgenic zebrafish model.

Fett, M.E., Pilsl, A., Paquet, D., Haass, C, Tatzelt, J., Schmid, B. and Winklhofer, K.F. (2010), PLoS One, 5 (7): e11783.

The novel membrane protein TMEM59 modulates complex glycosylation, cell surface expression and secretion of the amyloid precursor protein.

Ullrich, S., Muench, A., Neumann, S., Kremmer, E., Tatzelt, J. and Lichtenthaler, S.F. (2010), J Biol Chem, 285, 20664-20674.

Synthesis of a GPI anchor module suitable for protein posttranslational modification.

Schumacher M.C., Resenberger U., Seidel R.P., Becker C.F.W, Winklhofer K.F., Oesterhelt D., Tatzelt J. and Engelhard M. (2010), Biopolymers, 94, 457-464.

The Prion Protein.

Tatzelt J. (Editor) (2010), Book, Paperback, Savanna Press (January 1, 2010), ISBN: 0954333527

Alpha-helical domains promote translocation of intrinsically disordered polypeptides into the endoplasmic reticulum.

Miesbauer M., Pfeiffer N.V., Rambold A.S., Muller V., Kiachopoulos S., Winklhofer K.F. and Tatzelt J. (2009), J Biol Chem, 284, 24384-24393.

Loss of parkin or PINK1 function increases DRP1-dependent mitochondrial fragmentation.

Lutz A.K., Exner N., Fett M.E., Schlehe J.S., Kloos K., Laemmermann K., Brunner B., Kurz-Drexler A., Vogel F., Reichert A.S., Bouman L., Vogt-Weisenhorn D., Wurst W., Tatzelt J., Haass C. and Winklhofer K.F. (2009), J Biol Chem, 284, 22938-22951.

Green tea extracts interfere with the stress-protective activity of PrPC and the formation of PrPSc.

Rambold, A.S., Miesbauer, M., Olschewski, D., Riemer, C., Seidel, R., Smale, L., Brumm, L., Levy, M., Gazit, E., Oesterhelt, D., Becker, C.F.W., Engelhard M., Baier M., Winklhofer K.F. and Tatzelt J. (2008), J Neurochem, 107, 218–229.

Stress-protective signaling of prion protein is corrupted by scrapie-prions.

Rambold, A.S., Müller, V., Ron, U., Ben-Tal, N., Winklhofer K.F. and Tatzelt J. (2008), EMBO J, 27, 1974–1984.

Aberrant folding of pathogenic parkin mutants: aggregation versus degradation.

Schlehe, J.S., Lutz, A.K., Pilsl, A., Lämmermann, K., Grgur, K., Henn, I.H., Tatzelt, J., and Winklhofer, K.F. (2008), J Biol Chem, 283, 13771-13779.

A search for auxiliary proteins in prion replication.

Tamgüney, G., Giles, K., Glidden, D.V., Lessard, P., Wille, H., Tremblay, P., Groth, D., Yehiely, F., Korth, C., Moore, D.J., Tatzelt, J., Rubenstein, E., Boucheix, C., Stanley, P., Lisanti, M.P., Dwek, R.A., Rudd, P.M., Sisodia, S.S., Moskovitz, J., Epstein, C.J., Dawson Cruz, T.C., Kuziel, W.A., Maeda, N., Sap, J., Hsiao Ashe, K., Carlson, G.A., Tesseur, I., Wyss-Coray, T., Mucke, L., Weisgraber, K.H., Mahley, R.W., Cohen, F.E. and Prusiner, S.B. (2008), J Gen Virol, 89, 1777-1788.

Observing fibrillar assemblies on scrapie-infected cells.

Wegmann, S., Miesbauer, M., Winklhofer, K.F., Tatzelt, J., and Muller, D.J. (2008), Pflugers Arch, 456, 83-93.

The Prion Protein: Friend and Foe.

Tatzelt, J. (2009), Curr Issues Mol Biol, 12, 49-50.

Targeting of the prion protein to the cytosol: mechanisms and consequences.

Miesbauer M., Rambold A.S., Winklhofer K.F., Tatzelt J. (2009), Curr Issues Mol Biol, 12, 109-118.

The two faces of protein misfolding: Gain and loss of function in neurodegenerative diseases.

Winklhofer, K.F., Tatzelt, J., and Haass, C. (2008), EMBO J, 27, 336-49.

Semisynthetic murine Prion protein equipped with a GPI anchor mimic incorporates into cellular membranes.

Olschewski, D., Seidel, R., Miesbauer, M., Rambold, A.S., Oesterhelt, D., Winklhofer, K.F., Tatzelt, J., Engelhard, M., and Becker, C.F.W. (2007), Chem Biol, 14, 994-1006.

Parkin mediates neuroprotection through activation of IKK/NF-kB signaling.

Henn, I.H., Bouman, L., Schlehe, J.S., Schlierf, A., Schramm, J.E., Wegener, E., Nakaso, K., Culmsee, C., Berninger, B., Krappmann, D., Tatzelt, J., and Winklhofer, K.F. (2007), J Neurosci, 27, 1868-1878.

Association of Bcl-2 with misfolded prion protein is linked to the toxic potential of cytosolic PrP.

Rambold, A.S., Miesbauer, M., Rapaport, D., Bartke, T., Baier, M., Winklhofer, K.F., and Tatzelt, J. (2006), Mol Biol Cell, 17, 3356-3368.

Structural instability of the prion protein upon M205S/R mutations revealed by molecular dynamics simulations.

Hirschberger, T., Storck, M., Schropp, B., Winklhofer, K.F., Tatzelt, J. and Tavan, P. (2006), Biophys J, 90, 3908-3918.

Prion protein-related proteins from zebrafish are complex glycosylated and contain a glycosylphosphatidylinositol anchor.

Miesbauer, M., Bamme, T., Riemer, C., Oidtmann, B., Winklhofer, K.F., Baier, M. and Tatzelt, J. (2006), Biochem Biophys Res Commun, 341, 218-224.

Molecular basis of cerebral neurodegeneration in prion diseases.

Tatzelt, J*. and Schatzl, H.M*. (2007), FEBS J, 274, 606-611.
*corresponding authors

The role of chaperones in Parkinson's disease and prion diseases.

Winklhofer, K.F., and Tatzelt, J. (2006), In Handbook of Experimental Pharmacology, "Molecular chaperones in health and diseases", M. Gaestel, ed. (Springer-Verlag), Vol.172, 221-258.

Systematic identification of new anti-prion drugs by high-throughput screening based on scanning for intensely fluorescent targets (SIFT).

Bertsch, U., Winklhofer, K.F., T., H., Bieschke, J., Weber, P., Hartl, F.U., Tavan, P., Tatzelt, J., Kretzschmar, H.A. and Giese, A. (2005)., J Virol, 79, 7785-7791.

A pathogenic PrP mutation and doppel interfere with polarized sorting of the prion protein.

Uelhoff, A., Tatzelt, J., Aguzzi, A., Winklhofer, K.F. and Haass, C. (2005), J Biol Chem, 280, 5137-5140.

The polysaccharide scaffold of PrP 27-30 is a common compound of natural prions and consists of alpha-linked polyglucose.

Dumpitak, C., Beekes, M., Weinmann, N., Metzger, S., Winklhofer, K.F., Tatzelt, J. and Riesner, D. (2005), Biol Chem, 386, 1149-1155.

Pathogenic mutations inactivate parkin by distinct mechanisms.

Henn, I.H., Gostner, J.M., Tatzelt, J. and Winklhofer, K.F. (2005), J Neurochem, 92, 114-122.

Pathogenic mutations located in the hydrophobic core of the prion protein interfere with folding and attachment of the glycosylphosphatidylinositol anchor.

Kiachopoulos, S., Bracher, A., Winklhofer, K.F. and Tatzelt, J. (2005), J Biol Chem, 280, 9320-9329.

The structural transition of the prion protein into its pathogenic conformation is induced by unmasking hydrophobic sites.

Leffers, K.W., Schell, J., Jansen, K., Lucassen, R., Kaimann, T., Nagel-Steger, L., Tatzelt, J. and Riesner, D. (2004), J Mol Biol, 344, 839-853.

Misfolding of the prion protein at the plasma membrane induces endocytosis, intracellular retention and degradation.

Kiachopoulos, S., Heske, J., Tatzelt, J. and Winklhofer, K.F. (2004), Traffic, 5, 426-436.

The C-terminal domain of the prion protein is necessary and sufficient for import into the endoplasmic reticulum.

Heske, J., Heller, U., Winklhofer, K. F., and Tatzelt, J. (2004), J Biol Chem, 279, 5435-5443.

Folding and misfolding of the prion protein in the secretory pathway.

Tatzelt, J. and Winklhofer, K.F. (2004), Amyloid, 11, 162-172.

Inactivation of parkin by oxidative stress and C-terminal truncations; a protective role of molecular chaperones.

Winklhofer, K.F., Henn, I.H., Kay-Jackson, P., Heller, U. and Tatzelt, J. (2003), J Biol Chem, 278, 47199-47208.

Postranslational translocation of the prion protein into the endoplasmic reticulum interferes with cellular viability.

Heller, U., Winklhofer, K.F., Heske, J., Reintjes, A., and Tatzelt, J. (2003), J Biol Chem, 278, 36139-36147.

Inhibition of complex glycosylation increases formation of PrPSc.

Winklhofer, K.F., Heller, U., Reintjes, A. and Tatzelt, J. (2003), Traffic, 4, 313-322.

Determinants of the in vivo-folding of the prion protein: a bipartite function of helix 1 in folding and aggregation.

Winklhofer, K.F., Heske, J., Heller, U., Reintjes, A., Muranji, W., Moarefi, I. and Tatzelt, J. (2003), J Biol Chem, 278, 14961-14970.

A sensitive filter retention assay for the detection of PrPSc and the screening of anti-prion compounds.

Winklhofer, K.F., Hartl, F.U. and Tatzelt, J. (2001), FEBS Let, 503, 41-45.

Geldanamycin restores a defective heat shock response in vivo.

Winklhofer, K.F., Reintjes, A., Hoener, M.C., Voellmy, R. and Tatzelt, J. (2001), J Biol Chem, 276, 45160-45167.

Intracellular re-routing of prion protein prevents propagation of PrPSc and delays onset of prion diseases.

Gilch, S., Winklhofer, K.F., Nunziante, M., Lucassen, R., Spielhaupter, C., Muranyi, W., Groschup, M.H., Riesner, D., Tatzelt, J*. and Schätzl, H.M*. (2001), EMBO J, 20, 3957-3966.
*senior authors

Hohenheim consensus talks on Bovine Spongiform Encephalopathy (BSE).

Beyreuther, K., Biesalski, H.K., Dingermann, T., Kretzschmar, H.A., Multhaupt, G., Tatzelt, J. and Wolfram, G. (2002), Aktuel Ernaehr Med, 27, 304-314.

Inhibition of scrapie prion propagation.

Tatzelt*, J. and Winklhofer*, K.F. (2001), Gene Funct Dis, 2, 108-112.
*corresponding authors

Cationic lipopolyamines induce degradation of PrPSc in scrapie-infected mouse neuroblastoma cells.

Winklhofer, K.F. and Tatzelt, J. (2000), Biol Chem, 381, 463-469.

Kinetics of prion protein accumulation in the CNS of mice with experimental scrapie.

Tatzelt, J., Groth, D.F., Torchia, M., Prusiner, S.B. and DeArmond, S.J. (1999), J Neuropathol Exp Neurol, 58, 1244-1249.

Propagation of prion strains through specific conformers of the prion protein.

Scott, M.R., Groth, D., Tatzelt, J., Torchia, M., Tremblay, P., DeArmond, S.J. and Prusiner, S.B. (1997), J Virol, 71, 9032-9044.

A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis.

Schätzl, H.M., Laszlo, L., Holtzman, D.M., Tatzelt, J., DeArmond, S.J., Weiner, R.I., Mobley, W.C. and Prusiner, S.B. (1997), J Virol, 71, 8821-8831.

Prion protein expression in Chinese hamster ovary cells using a glutamine synthetase selection and amplification system.

Blochberger, T.C., Cooper, C., Peretz, D., Tatzelt, J., Griffith, O.H., Baldwin, M.A. and Prusiner, S.B. (1997), Protein Eng, 10, 1465-1473.

Chemical chaperones interfere with the formation of scrapie prion protein.

Tatzelt, J., Prusiner, S.B. and Welch, W.J. (1996), EMBO J, 15, 6363-6373.

Scrapie in mice deficient in apolipoprotein E or glial fibrillary acidic protein.

Tatzelt, J., Maeda, N., Pekny, M., Yang, S.-L., Betsholtz, C., Eliasson, C., Cayetano, J., Camerino, A.P., DeArmond, S.J. and Prusiner, S.B. (1996), Neurology, 47, 449-453.

Scrapie prions selectively modify the stress response in neuroblastoma cells.

Tatzelt, J., Zuo, J.R., Voellmy, R., Scott, M., Hartl, U., Prusiner, S.B. and Welch, W.J. (1995), Proc Natl Acad Sci U S A, 92, 2944-2948.

Abnormalities in stress proteins in prion diseases.

Tatzelt, J., Voellmy, R. and Welch, W.J. (1998), Cell Mol Neurobiol, 18, 721-729.

Fractionated nuclear extracts from hamster cells catalyze cell-free recombination at selective sequences between adenovirus DNA and a hamster preinsertion site.

Tatzelt, J., Fechteler, K., Langenbach, P. and Doerfler, W. (1993), Proc Natl Acad Sci U S A, 90, 7356-7360.

Recombination between adenovirus type 12 DNA and a hamster preinsertion sequence in a cell-free system. Patch homologies and fractionation of nuclear extracts.

Tatzelt, J., Scholz, B., Fechteler, K., Jessberger, R. and Doerfler, W. (1992), J Mol Biol, 228, 1275.

Recombination between adenovirus type 12 DNA and a hamster preinsertion sequence in a cell-free system. Patch homologies and fractionation of nuclear extracts.

Tatzelt, J., Scholz, B., Fechteler, K., Jessberger, R. and Doerfler, W. (1992), J Mol Biol, 226, 117-126.

The mechanism of adenovirus DNA integration: studies in a cell-free system.

Fechteler, K., Tatzelt, J., Huppertz, S., Wilgenbus, P. and Doerfler, W. (1995), Curr Top Microbiol Immunol, 199, 109-137.