Structure of beta-amyloid fibrils and its relevance to their neurotoxicity: implications for the pathogenesis of Alzheimer's disease.
Alzheimer's disease and cerebral amyloid angiopathy are characterized by the deposition of beta-amyloid fibrils consisting of 40- and 42-mer peptides (A beta 40 and A beta 42). Since the aggregation (fibrilization) of these peptides is closely related to the pathogenesis of these diseases, numerous structural analyses of A beta 40 and A beta 42 fibrils have been carried out. A beta 42 plays a more important role in the pathogenesis of these diseases since its aggregative ability and neurotoxicity are considerably greater than those of A beta 40. This review summarizes mainly our own recent findings from the structural analysis of A beta 42 fibrils and discusses its relevance to their neurotoxicity in vitro.
Irie
Kazuhiro
K
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan. irie@kais.kyoto-u.ac.jp
Murakami
Kazuma
K
Masuda
Yuichi
Y
Morimoto
Akira
A
Ohigashi
Hajime
H
Ohashi
Ryutaro
R
Takegoshi
Kiyonori
K
Nagao
Masaya
M
Shimizu
Takahiko
T
Shirasawa
Takuji
T
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D016229:Amyloid beta-Peptides; D009498:Neurotoxins