A CHEMICAL APPROACH TO ELUCIDATE THE MECHANISM OF TRANSTHYRETIN AND BETA-PROTEIN AMYLOID FIBRIL FORMATION

Amyloid deposits are associated with a variety of amyloid diseases, although their role in the pathogenesis remains unclear. Detection of amyloid fibrils and/or prevention of their formation appears to be important in the diagnosis and treatment of amyloid diseases such as Alzheimer's disease. The design of therapeutic molecules with this activity requires a detailed understanding of the structure of the amyloid fibril and the mechanism of fibril formation. This review is focused on studies carried out in the laboratories of the authors, who were trained as organic chemists and bring that perspective to their work. The ongoing studies described within have as their ultimate goal the complete description of the molecular mechanism of amyloid formation by two proteins; transthyretin and the amyloid beta protein. The purpose of this review is to outline chemical approaches and methodology which prove to be useful for understanding amyloid fibril formation.