Amyloid Fibrils and Cytotoxic Oligomers
Amyloidosis denotes a pathological condition characterized by fibrillar deposition of proteins and peptides. Up to date more than 25 human disorders have been linked to formation of amyloid. The fibrillar depositions may accumulate locally or systemic and depending on the associated protein as well as site of deposition, it can result in many different symptoms. The overall aim with our work is to understand the mechanism by which native, endogenous, polypeptides transforms into a pathological assembly and further to develop means for intervention. We focus on the complete chain of events spanning from a monomeric polypeptide to mature amyloid with a specific focus on the intermediate formation of oligomeric assemblies. Our established techniques involve recombinant expression and purification of proteins and peptides, CD, fluorescence, NMR, AFM, SPR, X-ray as well as immunological techniques. Moreover, using cell-based system for analysis of viability, correlations between structural properties and cytotoxic propensity can be made. Our work is focused on Familial Amyloidosis with Polyneuropathy as well as Alzheimer's and Parkinson's disease.