Novel approaches for studying amyloidogenic peptides/proteins

Abstract

A growing number of important human diseases are associated with the aggregation and deposition of incorrectly folded proteins in the form of highly structured amyloid fibrils. The aggregation process involves the formation of intermediate oligomeric assemblies with toxic properties. There are many commonalities among the different amyloid diseases, that is, similarities in structural features of amyloid fibrils or determinants of oligomer toxicity. Thus, a better knowledge of the general mechanisms of protein aggregation, the characterization of the aggregate's toxicity, and the identification of compounds interfering with these processes, may help for developing therapeutic strategies for different diseases. A variety of analytical methods are currently applied for these purposes. Here we focus on new applications of consolidated technologies which allow one to obtain informative data in a rapid and convenient manner. In particular, we discuss new applications of Surface Plasmon Resonance to study fibril elongation and to specifically recognize oligomers, as well as to screen for ligands of aggregated species and inhibitors of oligomer formation. We also review new advances in the use of wild-type or transgenic Caenorhabditis elegans as suitable in vivo models for the rapid and relatively inexpensive analysis of oligomer toxicity and for testing putative antagonists against this toxicity.