Objective "Beta-amyloid peptide, a component of senile plaques and generated by proteolytic cleavage of the amyloid precursor protein (APP), is a key factor in the pathogenesis of Alzheimer disease (AD). Beta-amyloid peptide has been shown to influence negatively some important mitochondrial activities such as reducing the efficiency of ATP-production via oxidative phosphorylation, enhancing mitochondrial ROS generation, and subsequently altering mitochondrial Ca2+ homeostasis. Based on these observations, it has been well established that mitochondrial dysfunctions and oxidative stress play an important role in the early pathology of Alzheimer disease. However, the molecular mechanisms linking beta-amyloid peptide to mitochondrial defects and to an increased oxidative stress leading to neurodegeneration in Alzheimer disease remain largely unknown.The main general goal of the proposed project is to assess the molecular impact of an increased accumulation of beta-amyloid peptide on mitochondrial protein homeostasis. The data collected from this project may provide crucial insights into AD etiology and pathogenesis.Specifically the following aspects will be determined:i) Effects on mitochondrial protein biogenesis: import and folding of nuclear encoded proteins, endogenous protein biosynthesis and complex assembly;ii) Identification of specific protein targets and the extent of protein post-translational modifications by increased levels of oxidative and nitrosative stress;iii) Adaptive response of mitochondrial protein quality control components establishing the potential of therapeutic intervention in the system.This project is expected not only to clarify the molecular mechanisms of beta-amyloid-induced mitochondrial dysfunctions in the pathogenesis of Alzheimer disease, but it will provide potential basis for the development of new AD therapies and for the identification of new candidates as biomarkers for early AD detection." Fields of science natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicineneurologydementiaalzheimernatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2011-IIF - Marie Curie Action: "International Incoming Fellowships" Call for proposal FP7-PEOPLE-2011-IIF See other projects for this call Funding Scheme MC-IIF - International Incoming Fellowships (IIF) Coordinator UNIVERSITATSKLINIKUM BONN Address Venusberg-campus 1 53127 Bonn Germany See on map Region Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Administrative Contact Beate Becker (Ms.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data
