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Project

Yeast-based models to study the Alzheimer's disease associated protein Pin 1.

Alzheimer's disease is the most prevalent neurodegenerative disorder. Since old age is one of the most important risk factors, the number of patients suffering from this disease is expected to increase dramatically over the coming years. So far, clinically available treatments are limited and mainly aimed at treating the symptoms. Alzheimer's disease is characterized by the presence of amyloid plaques and aggregates of protein tau in brain cells. This project will focus on the aggregation of protein tau which has been shown to be mainly caused by an incorrect phosphorylation of the protein. To gain a better insight in the mechanisms that regulate this phosphorylation we have developed a model system based on the baker's yeast Saccharomyces cerevisiae. This yeast model will be used to investigate the role of the peptidyl-prolyl isomerase Pin1 in more detail. Pin1 was shown to bind phosphorylation protein tau, thereby facilitating its dephosphorylation by the protein phosphatase PP2A. We will investigate this in our yeast model and study the influence of Pin1-mediated dephosphorylation on the different tau phospho-epitopes. Furthermore, we will also look at the role of Pin1 in stress-induced phosphorylation of protein tau, including stress induced by the peptide amyloid beta.
Date:1 Jan 2011 →  31 Dec 2012
Keywords:Yeast, Alzheimer's disease, Tau, Pin1, Phosphorylation, Aggregation
Disciplines:Biomaterials engineering, Biological system engineering, Biomechanical engineering, Other (bio)medical engineering, Environmental engineering and biotechnology, Industrial biotechnology, Other biotechnology, bio-engineering and biosystem engineering