Aggregation modulators of functional amyloids: silk fibroin as an inexpensive model for the investigation of the Alzheimer Disease pathogenesis - AMYLOIDS
Abstract: Aberrant protein aggregation, such as amyloidogenesis, is associated with many neurodegenerative diseases, such as Alzheimer’s disease. Most proteins can adopt an amyloid state, in which the protein backbone forms a cross-β-sheet structure capable of assembling into elongated unbranched ﬁbrils. Once misfolded, proteins can even cause the conversion of other folded proteins into amyloids, leading to both homotypic and heterotypic interactions. Heterotypic amyloid interactions have come into focus and cross-seeding seems to play a central role in the pathophysiological cascade of neurogegenerative disease. Silk fibroin (SF) is a physiological amyloid, that has been proven to be a good model to investigate amyloid aggregation and screen aggregation inhibitors. In this project SF will be studies to select small molecules and gold nanoparticles than can be transferred to pathological contexts. The issue of cross seeding, will be addressed through NMR interaction studies between SF and Ab.