Prof. Dr. Hermann LÜbbert, Animal Physiology, Faculty of Biology and Biotechnology

Hermann Lübbert

Research Programme:

The dopaminergic system in Parkinson's disease

In recent years we have seen considerable progress shedding light on some of the causes that can trigger the onset of the pathological cascade leading to Parkinson's disease in humans. Similar to the situation in most major diseases, the majority of cases has a multifactorial origin, a combination of genetic and environmental factors. About 5% of the patients carry mutations, which cause Parkinson's disease inherited in a Mendelian fashion, indicating that a single mutation is responsible for the disease.

At the Department of Animal Physiology we investigate the molecular cascade that is triggered by these factors and eventually leads to the pathological hallmarks of the disease, Lewy bodies and degeneration of dopaminergic neurons in the substantia nigra compacta. Multiple transgenic mouse lines have been constructed which carry human disease mutations either by over-expressing the mutated human protein (for dominantly inherited phenotypes) or through knock-out of the mouse gene (for recessively inherited phenotypes). In addition, several chemical toxins have been identified which cause Parkinson's disease in humans. We treat healthy or transgenic mice with these toxins and investigate the molecular consequences of this treatment.

The molecular cascade leading to disease is usually enhanced by self-reinforcing mechanisms. We investigate such mechanisms applying multiple technologies and approaches. (i) The temporal pattern of gene expression changes is analysed genome-wide using the DEPD technology. (ii) Interesting groups of genes are searched by Bioinformatics, applying a variety of clustering algorithms as well as neuronal and genetic networks. (iii) Genes that seem relevant for the disease process and their products are analysed further by in situ hybridisation, immunohistochemistry and functional assays.

Most graduate and diploma students are involved in projects covering aspect (iii).