Tham khảo tài liệu 'atomic force microscopy episode 2 part 8', kỹ thuật - công nghệ, cơ khí - chế tạo máy phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả | 26_ Atomic Force Microscopy of P-Amyloid Static and Dynamic Studies of Nanostructure and Its Formation Justin Legleiter and Tomasz Kowalewski 1. Introduction Ordered aggregation of the P-amyloid AP peptide in the brain as plaques consisting of fibrils is an important characteristic of Alzheimer s disease AD a late onset neurodegenerative disease 1 . AP derives from the endoproteolysis of the amyloid precursor protein APP which is a transmembrane protein containing 677-770 amino acids 2-9 . The two most common forms of AP are the 40 and 42 residues long fragments respectively referred to as AP 40 and AP 42 sequence shown in Fig. 1 ref. 10 . The insoluble aggregated form of AP which deposits in the extra cellular space in the brain and on the walls of cerebral blood vessels 6 exhibits an enhanced P-sheet conformation as opposed to the partially a-helical soluble form found in body fluids 11 12 . Despite the lack of the definitive establishment of the causative role of AP in AD evidence points to its aggregation and deposition in the pathogenesis of AD. The formation of the ordered P-sheet rich fibrils is believed to proceed via a slow nucleation-dependent mechanism that is followed by rapid chaingrowth into protofibrils that eventually elongate and possibly coalesce to form mature amyloid fibrils Fig. 2 refs. 7 13-17 . The elongation of the protofibrils and fibrils appears to be of the first order 7 13 16 17 . The slow step is the formation of AP oligomers that nucleate the process but it is unclear what causes the formation of these small oligomers. It appears that a critical local concentration needs to be achieved. Such conditions can occur as the result of inefficient clearance of AP from the brain. Intra- and extracellular surfaces located inside the brain could also play a pivotal role by increasing local concentrations of AP to facilitate the formation of a stable nucleus. Understanding how the process of fibrillogenesis is .
