Translational Neurodegeneration
Prof. Dr. Günter Höglinger
Head of clinical research Munich,
Group Leader
Feodor-Lynen-Str. 17
81377 München

guenter.hoeglinger@dzne.de
 +49 89 4400-46464

Areas of investigation/research focus

Our work focuses on akinetic-rigid Parkinson syndromes:

  • Diseases with pathological aggregation of alpha-synuclein (e.g. Parkinson’s Disease, Dementia with Lewy Bodies, Multisystem Atrophy)
  • Diseases with pathological aggregation of Tau-protein (e.g. Progressive Supranuclear Palsy, Cortico-Basal Degeneration).

The following areas of research have been established in our team:

  • Human genetic studies are performed to identify genetically determined risk factors for neurodegenerative diseases (Fig. 1).
  • Environmental risk factors for neurodegenerative diseases are being determined in experimental studies (Fig. 2).
  • Studies in experimental systems aim at the identification of molecular signals mediating neuronal dysfunction and degeneration (Fig. 3).
  • Cerebral repair processes, e.g. the generation of new neurons in the adult brain, and their potential to counteract neurodegenerative processes are being studied (Fig. 4).
  • Modern imaging modalities are applied to visualize pathological changes in the brains of living patients, aiming at the identification of disease mechanims and markers to ascertain diagnoses and to monitor progression (Fig. 5).
  • On the basis of the clinical and experimental observations, we aim to develop and refine pathophysiological disease concepts allowing to predict promising therapeutic targets, and finally to test these in clinical trials (e.g. Fig. 6).

Figures

 more Infos

Figure legends:
Fig. 1: Genetic risk factors: A Manhattan plot showing four newly identified, genetically determined risk factors for the neurodegenerative Tauopathy PSP (threshold P = 5x10-8). Note that the vertical axis is truncated at 10-15, but the P-value for MAPT on chromosome 17p is 10-116. [modified from Höglinger et al., Nature Genetics 2011;43:699-705].
Fig. 2: Environmental risk factors: Molecules which provoke a neurodegenerative Tauopathy in cultured neurons [from Höllerhage et al.; Exp Neurol. 2009;220:133-42].
Fig. 3: Neuronal cell death: Dopaminergic neurons (green) with axonal connection to the striatum (blue) activate a characteristic signal (red) during their demise [from Höglinger et al., Proc Natl Acad Sci U S A. 2007;104:3585–3590.].
Fig. 4: Brain repair: Neuronal stem cells (red) in the subventricular zone of the adult brain are proliferative (green) and embedded in a network of dopaminergic fibers (blue) [modified from Höglinger et al., Nature Neuroscience. 2004;7:726-735].
Fig. 5: Brain imaging: Cerebral PET study of PSP patients showing an upregulation of 5-HT2A receptors in the substantia nigra [from Stamelou et al., Movement Disorders, 2009;24:1170-5].
Fig. 6: Therapy development: Pathophysiological concept and putative therapeutic interventions (red) in Tauopathies [from Stamelou et al., Brain. 2010;133:1578-90].

Key Publications

Adam L Boxer, Jin-Tai Yu, Lawrence I Golbe, Irene Litvan, Anthony E Lang, Günter U Höglinger. Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches. The Lancet Neurology. 2017 Jun 30; 16:552-563. doi: 10.1016/S1474-4422(17)30157-6
Günter U. Höglinger, Gesine Respondek, Maria Stamelou, Carolin Kurz, Keith A. Josephs, Anthony E. Lang, Brit Mollenhauer, Ulrich Müller, Christer Nilsson, Jennifer L. Whitwell, Thomas Arzberger, Elisabet Englund, Ellen Gelpi, Armin Giese, David J. Irwin, Wassilios G. Meissner, Alexander Pantelyat, Alex Rajput, John C. van Swieten, Claire Troakes, Angelo Antonini, Kailash P. Bhatia, Yvette Bordelon, Yaroslau Compta, Jean-Christophe Corvol, Carlo Colosimo, Dennis W. Dickson, Richard Dodel, Leslie Ferguson, Murray Grossman, Jan Kassubek, Florian Krismer, Johannes Levin, Stefan Lorenzl, Huw R. Morris, Peter Nestor, Wolfgang H. Oertel, Werner Poewe, Gil Rabinovici, James B. Rowe, Gerard D. Schellenberg, Klaus Seppi, Thilo van Eimeren, Gregor K. Wenning, Adam L. Boxer, Lawrence I. Golbe, Irene Litvan, Adam L. Boxer, Alex Rajput, Alexander Pantelyat, Angelo Antonini, Anthony E. Lang, Armin Giese, Brit Mollenhauer, Carlo Colosimo, Caroline Kurz, Christer Nilsson, Claire Troakes, David J. Irwin, Dennis W. Dickson, Ellen Gelpi, Florian Krismer, Gerard D. Schellenberg, Gesine Respondek, Gil Rabinovici, Gregor K. Wenning, Günter U. Höglinger, Huw R. Morris, Irene Litvan, James B. Rowe, Jan Kassubek, Jean-Christophe Corvol, Jennifer L. Whitwell, Johannes Levin, John van Swieten, Kailash P. Bhatia, Keith A. Josephs, Klaus Seppi, Lawrence I. Golbe, Maria Stamelou, Murray Grossman, Peter Nestor, Richard Dodel, Stefan Lorenzl, Thilo van Eimeren, Thomas Arzberger, Ulrich Müller, Wassilios G. Meissner, Werner Poewe, Wolfgang H. Oertel, Yaroslau Compta, Yvette Bordelon. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Movement Disorders. 2017 May 31; 32:853-864. doi: 10.1002/mds.26987
Julius Bruch, Hong Xu, Thomas W Rösler, Anderson De Andrade, Peer-Hendrik Kuhn, Stefan F Lichtenthaler, Thomas Arzberger, Konstanze F Winklhofer, Ulrich Müller, Günter U Höglinger. PERK activation mitigates tau pathology in vitro and in vivo. EMBO Molecular Medicine. 2017 Feb 28; 9:371-384. doi: 10.15252/emmm.201606664
Günter U. Höglinger, Nadine M. Melhem, Dennis W. Dickson, Patrick M. A. Sleiman, Li-San Wang, Lambertus Klei, Rosa Rademakers, Rohan De Silva, Irene Litvan, David E. Riley, John C. Van Swieten, Peter Heutink, Zbigniew K. Wszolek, Ryan J. Uitti, Jana Vandrovcova, Howard I. Hurtig, Rachel G. Gross, Walter Maetzler, Stefano Goldwurm, Eduardo Tolosa, Barbara Borroni, Pau Pastor, Laura B. Cantwell, Mi Ryung Han, Allissa Dillman, Marcel P. Van Der Brug, J Raphael Gibbs, Mark R. Cookson, Dena G. Hernandez, Andrew B. Singleton, Matthew J. Farrer, Chang-En Yu, Lawrence I. Golbe, Tamas Revesz, John Hardy, Andrew J. Lees, Bernie Devlin, Hakon Hakonarson, Ulrich Müller, Gerard D. Schellenberg, Roger L. Albin, Elena Alonso, Angelo Antonini, Manuela Apfelbacher, Steven E. Arnold, Jesus Avila, Thomas G. Beach, Sherry Beecher, Daniela Berg, Thomas D. Bird, Nenad Bogdanovic, Agnita J. W. Boon, Yvette Bordelon, Alexis Brice, Herbert Budka, Margherita Canesi, Wang Zheng Chiu, Roberto Cilia, Carlo Colosimo, Peter P. De Deyn, Justo Garcãa De Yebenes, Laura Donker Kaat, Ranjan Duara, Alexandra Durr, Sebastiaan Engelborghs, Giovanni Fabbrini, Nicole A. Finch, Robyn Flook, Matthew P. Frosch, Carles Gaig, Douglas R. Galasko, Thomas Gasser, Marla Gearing, Evan T. Geller, Bernardino Ghetti, Neill R. Graff-Radford, Murray Grossman, Deborah A. Hall, Lili-Naz Hazrati, Matthias Höllerhage, Joseph Jankovic, Jorge L. Juncos, Anna Karydas, Hans A. Kretzschmar, Isabelle Leber, Virginia M. Lee, Andrew P. Lieberman, Kelly E. Lyons, Claudio Mariani, Eliezer Masliah, Luke A. Massey, Catriona A. McLean, Nicoletta Meucci, Bruce L. Miller, Brit Mollenhauer, Jens C. Möller, Huw R. Morris, Chris Morris, Sean S. O'Sullivan, Wolfgang H. Oertel, Donatella Ottaviani, Alessandro Padovani, Rajesh Pahwa, Gianni Pezzoli, Stuart Pickering-Brown, Werner Poewe, Alberto Rabano, Alex Rajput, Stephen G. Reich, Gesine Respondek, Sigrun Roeber, Jonathan D. Rohrer, Owen A. Ross, Martin N. Rossor, Giorgio Sacilotto, William W. Seeley, Klaus Seppi, Laura Silveira-Moriyama, Salvatore Spina, Karin Srulijes, Peter St. George-Hyslop, Maria Stamelou, David G. Standaert, Silvana Tesei, Wallace W. Tourtellotte, Claudia Trenkwalder, Claire Troakes, John Q. Trojanowski, Juan C. Troncoso, Vivianna M. Van Deerlin, Jean Paul G. Vonsattel, Gregor K. Wenning, Charles L. White, Pia Winter, Chris Zarow, Anna L. Zecchinelli. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nature Genetics. 2011 Jun 30; 43:699-705. doi: 10.1038/ng.859
Höglinger GU, Rizk P, Muriel MP, Duyckaerts C., Oertel WH, Caille I, Hirsch EC. Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nature Neuroscience. 2014 Jan 01; 7:726-735.

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