Correlation among Secondary Structure, Amyloid Precursor Protein Accumulation, and Neurotoxicity of Amyloid β(25-35) Peptide as Analyzed by Single Alanine Substitution

Kazuki Sato; Akiko Wakamiya; Tadakazu Maeda; Kaori Noguchi; Akihiko Takashima; Kazutomo Imahori

Kazuki Sato, Akiko Wakamiya, Tadakazu Maeda, Kaori Noguchi, Akihiko Takashima, Kazutomo Imahori

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Keywords: aggregation, amyloid β protein, β-sheet conformation, hydrophobicity, neurotoxicity

JOURNAL FREE ACCESS

1995 Volume 118 Issue 6 Pages 1108-1111

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Abstract

Structure-neurotoxicity relationships of amyloid β(25-35) peptide were studied by replacing each amino acid with Ala. In contrast to the general tendency in hydrophobicitytoxicity relationships, replacement of Asn²⁷ yielded a more hydrophobic but less toxic analog and that of Met³⁵ gave a less hydrophobic but more toxic one. Sedimentation profiles and CD spectra indicated that peptide aggregation via intermolecular β-sheet formation is essential for the neurotoxicity of amyloid β(25-35) peptide. The correlation between neurotoxicity and amyloid precursor protein accumulation suggested that the latter is one of the pathways of the neuronal death caused by amyloid β protein.

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