Correlation among secondary structure, amyloid precursor protein accumulation, and neurotoxicity of amyloid beta(25-35) peptide as analyzed by single alanine substitution.
Structure-neurotoxicity relationships of amyloid beta (25-35) peptide were studied by replacing each amino acid with Ala. In contrast to the general tendency in hydrophobicity-toxicity 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 beta-sheet formation is essential for the neurotoxicity of amyloid beta (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 beta protein.
Sato
K
K
Mitsubishi Kasei Institute of Life Sciences, Tokyo.
Wakamiya
A
A
Maeda
T
T
Noguchi
K
K
Takashima
A
A
Imahori
K
K
D000409:Alanine; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D017354:Point Mutation; D017433:Protein Structure, Secondary; D051381:Rats; D013329:Structure-Activity Relationship
D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D000409:Alanine