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).
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].