The turn formation at positions 22 and 23 in the 42‐mer amyloid β peptide: The emerging role in the pathogenesis of Alzheimer's disease

Kazuma Murakami1,2, Yuichi Masuda1, Takuji Shirasawa3, Takahiko Shimizu2, Kazuhiro Irie1
1Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan
2Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology,
3Department of Aging Control Medicine, Juntendo University Graduate School of Medicine, Tokyo, and

Tóm tắt

One hallmark of Alzheimer's disease (AD) is the accumulation of amyloid β (Aβ) peptides in the brain; Aβ mainly consists of 42‐mer and 40‐mer peptides (Aβ42 and Aβ40). Aβ42 plays a more critical role in the pathogenesis of AD because Aβ42 aggregates much faster and is more toxic than Aβ40. Therefore, there is an urgent need to elucidate the mechanism of aggregation and neurotoxicity of Aβ42 to develop therapeutic agents. Here, we introduce the pathological role of Aβ42 in AD and review our recent findings of the structural analysis of Aβ42 using systematic proline replacement, electron spin resonance and solid‐state nuclear magnetic resonance, and the new mechanism of neurotoxicity of Aβ42 through the formation of radicals. Geriatr Gerontol Int 2010; 10 (Suppl. 1): S169–S179.

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