Project Details
Projekt
Analysis of the structure and aggregation properties of natural and disease-related variants of the Alzheimer's Aß peptide (N01)
Subject Area
Cell Biology
Term
from 2007 to 2012
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5485142
Protein misfolding is a recognized cause of several human diseases. Specifically the formation of amyloidfibrils has also been implicated in a range of neurodegenerative disorders, with Alzheimer’s disease (AD) asthe most prominent one. AD amyloid fibrils are formed from β-amyloid peptide (Aβ), and they arise from ahighly complex formation process, involving numerous different conformational species. Aβ peptide naturallyoccurs with different sequential alloforms, such as the 40- and 42-residue peptides Aβ(1-40) and Aβ(1-42)and mutational variants associated with familial AD (FAD). In this project we aim (1) to gain better knowledgeabout the structure of Aβ amyloid fibrils. (2) We want to better understand the mechanism of Aβ fibrilformation and investigate the structural states occurring within the fibrillation process. (3) We seek to clarifythe effects of different amyloid structures on cells as well as the mechanism of amyloid formation within acellular context. (4) We want to analyse the effects of the different naturally occurring variations of chainlength and sequence mutation on the structure, aggregation behaviour and pathogenicity of Aβ. The centralhypothesis underlying this work - and to be tested here - is that pathogenicity of Aβ depends on specificconformational properties. Expected data will be relevant to understand better the molecular architecture ofaggregates and the structural basis of disease.
DFG Programme
Collaborative Research Centres
Applicant Institution
Universität Leipzig
Co-Applicant Institution
Martin-Luther-Universität Halle-Wittenberg; Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. (MPG)
Project Head
Professor Dr. Marcus Fändrich
