The effect of presenilin1 on PI3K- and mTor-pathways in neurons. A link to tauphosphorylation?

• Antragsteller: Dr. Volker Meske
• Fachliche Zuordnung: Molekulare Biologie und Physiologie von Nerven- und Gliazellen
• Förderung: Förderung von 2009 bis 2014
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 125194495

Two pathological features mark the brains of Alzheimer patients: amyloid plaques and neurofibrillary tangles. Amyloid plaques consist of aggregated amyloid-β protein, which is formed by a sequential action of β- and γ-secretase-mediated cleavage of the amyloid precursor protein. Neurofibrillary tangles consist of hyperphosphorylated protein tau which normally stabilizes neuronal cytoskeleton. Not yet fully understood is the metabolic link between the amyloid- and tau-pathology. There is increasing evidence that the insulin/PI3K-pathway plays an important role in the development of the Alzheimerpathology. In a cell-biological study we want to examine whether presenilin1, an important component of the γ-secretase-complex, influences enzymes of insulin/PI3K- and associated pathways. This is important as some of these enzymes are known to regulate the phosphorylation of tau-protein. Hence, the state of phosphorylation of tau-protein will serve as the disease-relevant marker in our investigations. The identification of crucial junctures, where amyloid-β- and tau-metabolism converge and influence each other, offers the possibility to develop new strategies in the medication of the disease.

• DFG-Verfahren: Sachbeihilfen
• Beteiligte Person: Professor Dr. Thomas Georg Ohm