کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1361233 981459 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Self-assembly pathways of E22Δ-type amyloid β peptide mutants generated from non-aggregative O-acyl isopeptide precursors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Self-assembly pathways of E22Δ-type amyloid β peptide mutants generated from non-aggregative O-acyl isopeptide precursors
چکیده انگلیسی

The recently identified E22Δ-type amyloid β peptide (Aβ) mutants are reported to favor oligomerization over fibrillization and to exhibit more-potent synaptotoxicity than does wild-type (WT) Aβ. Aβ(E22Δ) mutants can thus be expected to serve as tools for clarifying the impact of Aβ oligomers in Alzheimer’s disease (or Alzheimer’s-type dementia). However, the biochemical and biophysical properties of Aβ(E22Δ) have not been conclusively determined. Here, we evaluated the self-assembly pathways of Aβ(E22Δ) mutants generated from water-soluble, non-aggregative O-acyl isopeptide precursors. Circular dichroism spectroscopy, Western blot analysis, and thioflavin-T fluorescence intensity and cellular toxicity assays suggest that the self-assembly pathways of Aβ(E22Δ) differed from those of Aβ(WT). Aβ1–40(E22Δ) underwent a rapid random coil→β-sheet conformational change in its monomeric or low-molecular-weight oligomeric states, whereas Aβ1–40(WT) self-assembled gradually without losing its propensity to form random coil structures. The Aβ1–42(E22Δ) monomer formed β-sheet-rich oligomers more rapidly than did Aβ1–42(WT). Additionally, the Aβ1–42(E22Δ) oligomers appear to differ from Aβ1–42(WT) oligomers in size, shape, or both. These results should provide new insights into the functions of Aβ(E22Δ) mutants.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 12, 15 June 2011, Pages 3787–3792
نویسندگان
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