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

Kazuhiro Irie; Kazuma Murakami; Yuichi Masuda; Akira Morimoto; Hajime Ohigashi; Ryutaro Ohashi; Kiyonori Takegoshi; Masaya Nagao; Takahiko Shimizu; Takuji Shirasawa

doi:10.1263/jbb.99.437

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

Kazuhiro Irie, Kazuma Murakami, Yuichi Masuda, Akira Morimoto, Hajime Ohigashi, Ryutaro Ohashi, Kiyonori Takegoshi, Masaya Nagao, Takahiko Shimizu, Takuji Shirasawa

PHA - Molecular Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

85 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	437-447
Number of pages	11
Journal	Journal of Bioscience and Bioengineering
Volume	99
Issue number	5
DOIs	https://doi.org/10.1263/jbb.99.437
Publication status	Published - 2005 May

Keywords

Alzheimer's disease
Amyloid
Aβ40
Aβ42
Cerebral amyloid angiopathy
Familial Alzheimer's disease
Neurotoxicity
Oxidative stress
Solid-state nuclear magnetic resonance

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology

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10.1263/jbb.99.437

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title = "Structure of β-amyloid fibrils and its relevance to their neurotoxicity: Implications for the pathogenesis of Alzheimer's disease",

abstract = "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.",

keywords = "Alzheimer's disease, Amyloid, Aβ40, Aβ42, Cerebral amyloid angiopathy, Familial Alzheimer's disease, Neurotoxicity, Oxidative stress, Solid-state nuclear magnetic resonance",

author = "Kazuhiro Irie and Kazuma Murakami and Yuichi Masuda and Akira Morimoto and Hajime Ohigashi and Ryutaro Ohashi and Kiyonori Takegoshi and Masaya Nagao and Takahiko Shimizu and Takuji Shirasawa",

note = "Funding Information: We thank Drs. Hiroyuki Fukuda and Mayumi Shindo of Applied Biosystems Japan, Ltd., for MALDI-TOF-MS measurements, Mr. Naoto Kanbayashi at Jasco Engineering for the ATR-FTIR measurement, and Dr. Naotaka Izumiyama-Shimomura at Human Tissue Research Group of Tokyo Metropolitan Institute of Gerontology for the electron microscope. This research was supported in part by Grants-in-Aid for Scientific Research (B) (no. 13460048 and 16380080 to K.I.), Special Coordination Funds (to H.O.), and a Grant-in-Aid for the Promotion of Science for Young Scientists (to K.M.) from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese Government.",

year = "2005",

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doi = "10.1263/jbb.99.437",

language = "English",

volume = "99",

pages = "437--447",

journal = "Journal of Bioscience and Bioengineering",

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TY - JOUR

T1 - Structure of β-amyloid fibrils and its relevance to their neurotoxicity

T2 - Implications for the pathogenesis of Alzheimer's disease

AU - Irie, Kazuhiro

AU - Murakami, Kazuma

AU - Masuda, Yuichi

AU - Morimoto, Akira

AU - Ohigashi, Hajime

AU - Ohashi, Ryutaro

AU - Takegoshi, Kiyonori

AU - Nagao, Masaya

AU - Shimizu, Takahiko

AU - Shirasawa, Takuji

N1 - Funding Information: We thank Drs. Hiroyuki Fukuda and Mayumi Shindo of Applied Biosystems Japan, Ltd., for MALDI-TOF-MS measurements, Mr. Naoto Kanbayashi at Jasco Engineering for the ATR-FTIR measurement, and Dr. Naotaka Izumiyama-Shimomura at Human Tissue Research Group of Tokyo Metropolitan Institute of Gerontology for the electron microscope. This research was supported in part by Grants-in-Aid for Scientific Research (B) (no. 13460048 and 16380080 to K.I.), Special Coordination Funds (to H.O.), and a Grant-in-Aid for the Promotion of Science for Young Scientists (to K.M.) from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese Government.

PY - 2005/5

Y1 - 2005/5

N2 - 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.

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KW - Amyloid

KW - Aβ40

KW - Aβ42

KW - Cerebral amyloid angiopathy

KW - Familial Alzheimer's disease

KW - Neurotoxicity

KW - Oxidative stress

KW - Solid-state nuclear magnetic resonance

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

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