Molecular Mechanisms in the Regulation of Metabolism and Biological Functions of the ß-Amyloid Precursor Protein

• Applicant: Professor Jochen Walter, Ph.D.
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2002 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5380957

Alzheimer's disease is a neurodegenerative, age-dependent disorder, pathologically characterized by the accumulation of extracellular amyloid plaques in specific regions of the brain. A major constituent of amyloid plaques is the amyloid ß-peptide (Aß), which derives from the ß-amyloid precursor protein (ßAPP) by proteolytic processing. In the secretory pathway ßAPP undergoes phosphorylation within its lumenal/ecto-domain. We recently identified the phosphorylation sites of ßAPP and two candidate protein kinases which can phosphorylate ßAPP. Moreover, we could demonstrate that phosphorylation of ßAPP can occur at two distinct subcellular compartments. Based on these results we now want to investigate the biological function of this unusual phosphorylation event. We first will focus on the effect of ßAPP phosphorylation on its proteolytic processing, and the generation of Aß. In addition, the role of phosphorylation on the intracellular transport of ßAPP, on the binding of ßAPP ligands and on cell adhesion, especially on neurite outgrowth, will be investigated.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1085: Cellular Mechanisms of Alzheimer's Disease