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Investigation of Beta-Amyloid Peptide Effects On Mitochondria Protein Homeostasis: From Pathogenesis to Therapy of Alzheimer Disease


Start Date
End Date
Total Funding
€ 167 390
Funding Programme
European Countries Involved

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.'

Project partners

Universitatsklinikum Bonn

Alzheimer Europe's database on research projects was developed as part of the 2020 Work Plan which received funding under an operating grant from the European Union’s Health Programme (2014–2020).