Dr. Kretzschmar received her Ph.D. from the University of Wüerzburg, Germany. She completed postdoctoral programs at the University of Southern California Medical School and the California Institute of Technology. Before joining CROET, she was a Group Leader, University Regensburg and University Wüerzburg, Germany.

We are using Drosophila melanogaster to study basic mechanisms of neurodegeneration in occupational and other diseases. One approach, is to isolate and characterize Drosophila mutants with age-dependent degeneration of the nervous system. One mutant called swiss-cheese, encodes a protein that is homologous to the human Neuropathy Target Esterase, a key target of organophosphate pesticides. Other mutants encode proteins involved in microtubule formation and cholesterol homeostasis, both processes having been shown to play an important role in Alzheimer's disease (AD). Interestingly these mutants influence the processing of the Amyloid Precursor Protein, a key protein in the pathogenesis of AD. To investigate APP, its function, and its role in Alzheimer's disease, we have establish a Drosophila model revealing key features of AD, like plaque formation, behavioral deficits, and neuronal cell death. These models allow us to investigate mechanisms underlying common neurodegenerative diseases.

One of our main efforts now is to isolate interaction partners for these genes by genetic and molecular means. We can then investigate the pathways leading to neurodegeneration in our experimentally easy accessible model system. The possible transfer of results to vertebrates will then hopefully lead to the understanding of human neurodegenerative diseases.

Dr. Kretzschmar's Lab

D. Kretzschmar. Neurodegenerative mutants in Drosophila: a means to identify genes and mechanisms involved in human diseases? Invertebrate Neuroscience, 5, 97-109, 2005.

A. Bettencourt da Cruz, M. Schwärzel, S. Schulze, M. Niyyati, M. Heisenberg and D. Kretzschmar. Disruption of the microtubule-associated protein FUTSCH leads to progressive degeneration in Drosophila. Molecular Biology of the Cell, 16, 2433-2442, 2005.

M. Muehlig-Versen, A. Bettencourt da Cruz, J.-A. Tschaepe, M. Moser, R. Buettner, K. Athenstedt, P. Glynn and D. Kretzschmar. Loss of Swiss Cheese/Neuropathy Target Esterase activity causes disruption of phophatidylcholine homeostasis and neuronal and glial death in adult Drosophila. Journal of Neuroscience, 25, 2865-2873, 2005.

J.A. Botella, J.K. Ulschmid, C. Grünewald, C. Möhle, D. Kretzschmar, K. Becker and S. Schneuwly. The Drosophila carbonyl reductase sniffer prevents oxidative stress-induced neurodegeneration. Current Biology, 14, 782-786, 2004.

I. Greeve, D. Kretzschmar, J. Tschäpe, A. Beyn, C. Brellinger, M. Schweizer, R. Nitsch and R. Reifegerste. Alzheimer's disease-like neuropathology in transgenic Drosophila. Journal of Neuroscience, 24, 3899-3906, 2004.

J.-A. Tschäpe, A. Bettencourt da Cruz, and D. Kretzschmar. Progressive neurodegeneration in Drosophila: a model system. Journal of Neural Transmission, Suppl. 65, 105-116, 2003.

J.A. Botella, D. Kretzschmar, C. Kiermayer, P. Feldmann. D.A. Hughes and S. Schneuwly. Deregulation of the Egfr/Ras signaling pathway induces age-related brain degeneration in the Drosophila mutant vap. Molecular Biology of the Cell, 14, 241-250., 2003.

J.-A. Tschäpe, C. Hammerschmied, M. Mühlig-Versen, K. Athenstaedt, G. Daum and D. Kretzschmar. The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and Appl processing. The EMBO Journal, 21, 2002.

Dr. Kretzschmar on PubMed