Prof. Dr. Günter U. Höglinger

Group Leader

German Center for Neurodegenerative Diseases (DZNE)
Max Lebsche Platz 30
81377 Munich

guenter.hoeglinger(at)dzne.de
+49 (0) 89 / 7095-8406 (Office)
+49 (0) 89 / 2180-75469 (Assistant)
+49 (0) 89 / 2180-75432

More information

Group Members Curriculum Vitae
Homepage Cooperation partner  

Areas of investigatins/research focus

We aim to tightly link disease-oriented basic science with clinical research, in an attempt to develop new diagnostic and therapeutic options for neurodegenerative diseases, based on new scientific concepts. Therefore, we transfer results from clinical research to refine experimental disease models (from bed to bench). Inversely, we aim to translate results from experimental research into innovative clinical trials (from bed to bench).

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).
Click on the magnifying glass for a large image.
Fig. 1
Click on the magnifying glass for a large image.
Fig. 2
Click on the magnifying glass for a large image.
Fig. 3
Click on the magnifying glass for a large image.
Fig. 4
Click on the magnifying glass for a large image.
Fig. 5
Click on the magnifying glass for a large image.
Fig. 6

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].


Publications (Selection)

Identification of common variants influencing risk of the tauopathy Progressive Supranuclear Palsy.

Höglinger GU, Melhem NM, Dickson DW, Sleiman PMA, Wang LS, Klei L, Rademakers R, de Silva R, Litvan I, Riley DE, van Swieten JC, Heutink P, Wszolek ZK, Uitti RJ Vandrovcova J, Hurtig HI, Gross RG, Maetzler W, Goldwurm S, Tolosa E, Borroni B, Pastor P, PSP Genetics Study Group, Cantwell LB, Han MR, Dillman A, van der Brug MP, Gibbs JR, Cookson MR, Hernandez DG, Singleton AB, Farrer MJ, Yu CE, Golbe LI, Revesz T, Hardy J, Lees AJ, Devlin B, Hakonarson H, Müller U, Schellenberg JD. Nature Genetics, 2011;43:699-705.

Microglial glucocorticoid receptors play a pivotal role in regulating dopaminergic neurodegeneration in parkinsonism.

Ros-Bernal F, Hunot S, Herrero MT, Parnadeau S, Corvol JC, Lu L, Alvarez-Fischer D, Carrillo MA, Saurini F, Coussieu C, Kinugawa K, Prigent A, Höglinger G, Hamon M, Tronche F, Hirsch EC, Vyas S.  Proc Natl Acad Sci U S A, 2011;108:6632-7.

Systemic administration of Neuregulin-1ß1 protects dopaminergic neurons in a model of Parkinson’s disease.

Carlsson T, Schindler FR, Höllerhage M, Depboylu C, Arias-Carrión O, Schnurrbusch S, Rösler TW, Wozny W, Schwall GP, Groebe K, Oertel WH, Brundin P, Schrattenholz A, Höglinger GU.  J. Neurochemistry. 2011;117:1066-74.

Hypodipsia discriminates progressive supranuclear palsy from other parkinsonian syndromes.

Stamelou M, Christ H, Reuss A, Oertel WH, Höglinger GU.  Mov Disord. 2011;26:901-5.

Health-related quality of life in Multiple System Atrophy and Progressive Supranuclear Palsy.

Winter Y, Stamelou M, Cabanel N, Sixel-Döring F, Eggert K, Höglinger GU; Herting B, Klockgether T, Reichmann H, Oertel WH, Dodel R, Spottke A. Neurodegenerative Diseases. 2011;8:438-46.

Rational therapeutic approaches to progressive supranuclear palsy.

Stamelou M, de Silva R, Arias-Carrion O, Boura E, Höllerhage M, Oertel WH, Müller U, Höglinger GU.  Brain. 2010;133:1578-90.

Possible Involvement of Complement Factor C1q in the Clearance of Extracellular Neuromelanin from the Substantia Nigra in Parkinson’s Disease.

Depboylu C, Schäfer MKH, Arias-Carrión O, Oertel WH, Weihe E, Höglinger GU.  J Neuropath Exp Neurology. 2011;70:125-32.

In vivo demonstration of microstructural brain pathology in progressive supranuclear palsy: A DTI study using TBSS.

Knake S, Belke M, Menzler K, Pilatus U, Eggert KM, Oertel WH, Stamelou M, Höglinger GU.  Mov Disord. 2010;25:1232-8.

Natural lipophilic inhibitors of mitochondrial complex I are candidate toxins for sporadic neurodegenerative tau pathologies.

Höllerhage M, Matusch A, Champy P, Lombès A, Ruberg M, Oertel WH, Höglinger GU. Exp Neurol. 2009;220:133-42.

In vivo evidence for cerebral depletion in high-energy phosphates in progressive supranuclear palsy.

Stamelou M, Pilatus U, Reuss A, Magerkurth J, Eggert KM, Knake S, Ruberg M, Schade-Brittinger C, Oertel WH, Höglinger GU. J Cerebral Blood Flow Metabolism, 2009;29:861-70.

Nigrostriatal upregulation of 5-HT2A receptors in progressive supranuclear palsy.

Stamelou M, Matusch A, Elmenhorst D, Hurlemann R, Eggert KM, Zilles K, Oertel WH, Höglinger GU*, Bauer A*. * equal contribution, Movement Disorders, 2009;24:1170-5.

Short-term effects of coenzyme Q10 in progressive supranuclear palsy: a randomized, placebo-controlled trial.

Stamelou M, Reuss A, Pilatus U, Magerkurth J, Niklowitz P, Eggert KM, Krisp A, Menke T, Schade-Brittinger C, Oertel WH, Höglinger GU.  Movement Disorders, 2008;23:942-9.

Annonacin, a Natural Mitochondrial Complex I Inhibitor, Causes Tau Pathology in Cultured Neurons.

Escobar Khondiker M, Höllerhage M, Michel PP, Muriel MP, Champy P, Respondek G, Yagi T, Lannuzel A, Hirsch EC, Oertel WH, Jacob R, Ruberg R, Höglinger GU.  J. Neuroscience. 2007;27:7827-37.

The pRb/E2F cell-cycle pathway mediates cell death in Parkinson’s disease.

Höglinger GU, Breunig JJ, Depboylu C, Rouaux C, Michel PP, Alvarez-Fischer D, Boutillier AL, DeGregori J, Oertel WH, Rakic P, Hirsch EC, Hunot S. Proc Natl Acad Sci U S A. 2007;104:3585–3590.

Atypical Parkinsonism in Guadeloupe: a common risk factor for two closely related phenotypes?

Lannuzel A, Höglinger GU, Verhaeghe S, Gire L, Belson S, Escobar-Khondiker M, Poullain P, Oertel WH, Hirsch EC, Dubois B, Ruberg M. Brain. 2007;130:816-27.

New striatal dopamine neurons in MPTP-treated macaques result from a phenotypic shift not neurogenesis.

Tandé D, Höglinger GU, Debeir T, Freundlieb N, Hirsch EC, François C.  Brain. 2006;129:1194–1200.

Dopaminergic Substantia Nigra Neurons Project Topographically Organized to the Subventricular Zone and Stimulate Precursor Cell Proliferation in Aged Primates.

Freundlieb N, François C, Tandé D, Oertel WH, Hirsch EC, Höglinger GU.  J. Neuroscience. 2006;26:2321-2325.

Evaluation of a screening procedure for the early diagnosis of Parkinsonism at the level of general practitioners.

Höglinger GU, Rissling I, Ries V, Heinermann A, Baum E, Deuschl G, Spieker S, Oertel WH.  Movement Disorders. 2004;19:505-512.

Dopamine depletion impairs precursor cell proliferation in Parkinson disease.

Höglinger GU, Rizk P, Muriel MP, Duyckaerts C., Oertel WH, Caille I, Hirsch EC. Nature Neuroscience. 2004;7:726-735.