Synthetic post-translationally modified human Aβ peptide exhibits a markedly increased tendency to form β-pleated sheets in vitro

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DOIResolve DOI: http://doi.org/10.1111/j.1432-1033.1994.tb18811.x
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TypeArticle
Journal titleEuropean Journal of Biochemistry
Volume221
Issue3
Pages959964; # of pages: 6
AbstractThe β-amyloid peptide (Aβ) is the major constituent of senile plaques, one of the hallmark neuropathological lesions of Alzheimer's disease. Recently a post-translationally modified analogue of the human β-amyloid peptide, which contains isoaspartatic residues in positions 1 and 7, was isolated from parenchyma and leptomeningeal microvasculature of Alzheimer's disease patients [Roher, A. E., Lowenson, JD., Clarke, S., Wolkow, C., Wang, R., Cotter, R. J., Reardon, I. M., Zürcher-Neely, H. A., Heinrikson, R. L., Ball, M. J. & Greenberg, B. D. (1993) J. Biol. Chem. 268, 3072–3083]. We used circular dichroism and Fourier-transform infrared spectroscopy to characterize the conformational changes on human Aβ upon substitution of Asp1 and Asp7 to isoaspartic residues. We found that the intermolecular β-pleated-sheet content is markedly increased for the post-translationally modified peptide compared to that in the corresponding unmodified human or rodent Aβ sequences both in aqueous solutions in the pH 7–12 range, and in membrane-mimicking solvents (such as aqueous octyl-β-d-glucoside or aqueous acetonitrile solutions). These findings underline the importance of the originally α-helical N-terminal regions of the unmodified Aβ peptides in defining its secondary structure and may offer an explanation for the selective aggregation and retention of the isomerized Aβ peptide in Alzheimer's-disease-affected brains.
Publication date
PublisherFEBS
LanguageEnglish
AffiliationNational Research Council Canada; NRC Institute for Biodiagnostics
Peer reviewedYes
NRC number153
NPARC number9148530
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Record identifier256d45f6-0b68-4447-9918-eed47da553e4
Record created2009-06-25
Record modified2016-12-08
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