MOLECULAR RECOGNITION AND SELF-ASSEMBLY OF AMYLOID FIBRILS: THE ROLE OF AROMATIC INTERACTIONS

摘要

The formation of amyloid fibril plaques is associated with major diseases of unrelated origin. A partial list includes Alzheimer's diseases, Parkinson's disease, Type II diabetes, Prion diseases, and various familial amyloidosis diseases. The mechanism of amyloid fibrils formation is assumed to be a nucleation-dependent process. According to the common models, unfolding events are followed by a series of equilibrium steps to form a prefibrillar nucleus of a critical size. This is followed by therrnodynamically-favorable growth steps of addition of monomers to the growing nucleus. In all these cases normal proteins undergo a self-organization process that result in the formation of well-ordered assemblies with fibrilar structure and a diameter of 7-10 nm, as observed by electron microscopy and atomic force microcopy, and a clear X-ray fiber diffraction with a 4.6-4.8 A reflection on the meridian. However, in spite of the key medical importance of the process of amyloid self-assembly, the molecular mechanism by which amyloid fibrils are being formed is not fully understood.