Structure of β-amyloid fibrils and its relevance to their neurotoxicity: Implications for the pathogenesis of Alzheimer’s disease

• Published in: Journal of bioscience and bioengineering 2005-05, Vol.99 (5), p.437-447
• Main Authors: Irie, Kazuhiro, Murakami, Kazuma, Masuda, Yuichi, Morimoto, Akira, Ohigashi, Hajime, Ohashi, Ryutaro, Takegoshi, Kiyonori, Nagao, Masaya, Shimizu, Takahiko, Shirasawa, Takuji
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Alzheimer’s disease; Amino Acid Sequence; amyloid; Amyloid beta-Peptides - analysis; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Animals; Aβ40; Aβ42; Biological and medical sciences; Biotechnology; cerebral amyloid angiopathy; familial Alzheimer’s disease; Fundamental and applied biological sciences. Psychology; HUMAN DISEASES; Humans; Models, Biological; Models, Chemical; Models, Molecular; Molecular Sequence Data; NEUROPHYSIOLOGY; neurotoxicity; Neurotoxins - chemistry; Neurotoxins - metabolism; NMR SPECTROSCOPY; oxidative stress; PEPTIDES; Protein Conformation; solid-state nuclear magnetic resonance; STRESS; Structure-Activity Relationship
• ISSN: 1389-1723; 1347-4421
• DOI: 10.1263/jbb.99.437

Alzheimer’s disease and cerebral amyloid angiopathy are characterized by the deposition of β-amyloid fibrils consisting of 40- and 42-mer peptides (Aβ40 and Aβ42). Since the aggregation (fibrilization) of these peptides is closely related to the pathogenesis of these diseases, numerous structural analyses of Aβ40 and Aβ42 fibrils have been carried out. Aβ42 plays a more important role in the pathogenesis of these diseases since its aggregative ability and neurotoxicity are considerably greater than those of Aβ40. This review summarizes mainly our own recent findings from the structural analysis of Aβ42 fibrils and discusses its relevance to their neurotoxicity in vitro.