|Name||Sascha Norbert Lange
|Place of birth||Hamburg|
|Date of birth||20.11.1970|
PhD student at the Institute for Neuropathology, University Medical Center Hamburg-Eppendorf
|2005/2006||Research associate, Bone marrow transplantation unit, University Medical Center Hamburg-Eppendorf|
|2004/2005||B. Diploma thesis at the Centre for Molecular Neurobiology Hamburg
Institute for Molecular Neuropathology
|2000-2004||Studies in biochemistry and molecular biology in Hamburg
|1997-2000||Vocational training as biology lab assistant at the Fraunhofer Arbeitsgruppe für Toxikologie und Umweltmedizin, Hamburg
Mechanisms of protein degradation in dementia
Currently in Germany over one million people suffer from dementia. According to estimates by the World Health Organisation, dementias such as Alzheimer´s Disease the fourth most common cause of death among people older than sixty years.
The exact causes for dementia are poorly understood.However, it is assumed that dementias share common pathways. Neuronal accu- mulation of malprocessed proteins is the hallmark of a number of neurodegenerative disorders such as diffuse Lewy body disease, tauopathies and familial encephalopathy with neuroserpin inclusion bodies (FENIB). Accumulation of malprocessed proteins is a dynamic process, resulting in the disturbed balance between synthesis and degradation. The result is protein aggregation in the cells, as the cause of a subsequent dementia. The familial encephalopathy with neuro- serpin inclusion bodies (FENIB) is an inherited disease of the brain that causes demantia already in the early stages of life.
A protein that is very similar to the neuroserpin is found in the nematode Caenorhabditis elegans (C. elegans). Through changes in the naturally occurring protein, it is possible to mimic the disease and analyse it. In the living worm single proteins can be switched off and thus signal paths, that might play a role in neuroserpin-interaction be elucidated. In the living organism it is also possible to test certain substances that prevent or delay the beginning of the aggregation.
The objective of my PhD thesis is to identify components involved in the degradation of aggregated neuronal proteins. For this, we have gene- rated a C. elegans based model of FENIB employing fluorescently tagged, aggregation-prone forms of neuroserpin. This allows for high throughput screens and subsequent isolation of new genes and pharmacological substances modulating degradation of aggregated neuroserpin. These studies will be extended to mammalian cell culture and in a murine model system. Data from these studies will be valuable in identifying pathways of protein degradation in neurodegeneration.