|Place of birth||Münster, Germany|
|Date of birth||08/05/1977|
|since 2005||Ph.D. Student, Molecular Cellbiology AG prof. Dr. Jochen Walter, University of Bonn|
|2003/2004||Diploma thesis "Functional Analysis of the middle domain of the molecular Chaperone Hsp90 with molecularbiological and biochemical methods", Protein Folding Group AG Dr. Wolfgang Obermann, Institute for Genetics, university of Bonn|
|1998-2004||Universities of Darmstadt and Bonn, Diploma in Biology|
Molecular Mechanisms in the Regulation of Neprilysin
Accumulation of the amyloid ß-peptide (Aß) is a common neuropathological feature of Alzheimer`s disease (AD). Aß derives from proteolytic processing of the ß-amyloid precursor protein (ßAPP) involving at least two distinct membrane bound proteases. Aß levels in the brain are not only determined by the activity of proteases involved in its generation, but also by enzymes able to degrade this peptide. Several zinc-metalloproteases have been shown to cleave Aß, including the insulin degrading enzyme, the endothelin-converting enzymes-1 and -2 and the type II membrane protein neprilysin (NEP).
Accordingly increased expression of NEP activity results in enhanced degradation of Aß and decreased Aß deposition.
This PhD project aims to identify molecular mechanisms that regulate the subcellular trafficking and activity of NEP. By using biochemical and cell biological approaches, specifically the role of phosphory- lation in the regulation of NEP metabolism and NEP localisation are investigated. Initial studies demonstrated that NEP is phosphorylated in vitro and in vivo and I am now focusing on the characterisation of the underlying signalling pathways, including the identification of protein kinases that phosphorylate NEP and the respective phosphorylation sites.
Since previous investigations showed that somatostatin signalling affects NEP activity and localisation, the involvement of NEP phosphorylation in these processes will be investigated. This research project should lead to novel insights into the regulation of NEP, its Aß degrading ability and allow the identification and evaluation of potential approaches to decrease Aß levels in the brain as therapeutic strategies for the treatment of Alzheimer's disease.