Ruediger Klein, PhD

Parkinson's disease results largely from the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The reason for the successive death of these neurons is not known so far. Experiments on mature neurons in culture and on animals with brain injuries support the notion that neurotrophic factors are important for survival of neurons in the adult brain. Pharmacological and in vitro studies have shown promising effects on survival of dopaminergic neurones, especially for the neurotrophic factors brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). However, the endogenous survival factors for dopaminergic neurons during postnatal development and in adulthood have not been determined. Knowledge about the endogenous neurotrophic factors for dopaminergic neurons will allow us to evaluate and to improve potential neurotrophic therapies for the treatment of Parkinson's disease. Neurotrophic factors bind to cells via specific receptors, which float on the cell surface and stretch out an antenna-like sensor away from the cell. We will use modern genetic tools to disrupt expression of the receptors for BDNF and GDNF in an in vivo mouse model. To avoid deleterious effects on other neuron populations and during development of the mice, we will limit the deficiency in space (dopaminergic neurons) and time (postnatal stages). We expect that in the absence of these receptors, dopaminergic neurons will loose dopaminergic functions, shrink, and eventually die. These experiments will for the first time test, if BDNF and GDNF-family of growth factors are required for dopaminergic neurons in vivo, or whether other trophic factors and their receptors play more important roles. The newly generated transgenic mice will also allow us to inducibly delete or overexpress genes specifically in dopaminergic neurons and test their importance concerning survival and function.

Dr. Ruediger Klein was born March 24, 1958, in Nickenich, Germany. He completed studies in Biology at the Philipps University Marburg, Juniata College, USA, Eberhard-Karls-University Tuebingen, earning a PhD in 1987. He did research abroad at the Frederick Cancer Research and Development Center in Frederick, Maryland, and Bristol-Myers Squibb Pharmaceutical Research Institute in Princeton, New Jersey (1988-1993). Positions held include Group Leader at the European Molecular Biology Laboratory, Heidelberg, Germany (1993-2001) and Director and Scientific Member of the Max-Planck-Institute of Neurobiology (since 2001). Dr. Klein is also an elected member of the European Molecular Biology Organization (EMBO) (1998) and a Member of the American Society for Neuroscience.