https://scholars.lib.ntu.edu.tw/handle/123456789/569468
標題: | An improved screening model to identify inhibitors targeting zinc-enhanced amyloid aggregation | 作者: | Chang P.-T. FAN-LU KUNG Talekar R.S. Chen C.-S. Lai S.-Y. Lee H.-Y. Chern J.-W. |
公開日期: | 2009 | 卷: | 81 | 期: | 16 | 起(迄)頁: | 6944-6951 | 來源出版物: | Analytical Chemistry | 摘要: | Zinc, which is abundant in senile plaques consisting mainly of fibrillar β-amyloid (Aβ), plays a critical role in the pathogenesis of Alzheimer's disease. Treatment with zinc chelators such as clioquinol has been used to prevent Aβ aggregation in Alzheimer's patients; however, clioquinol produces severe side effects. A simple, easy, inexpensive, and versatile screen to identify zinc chelators for inhibition of Aβ aggregation is currently unavailable. We thus developed a high-throughput screen that identi-fies zinc chelators with anti-Aβ aggregation activity. The recombinant Aβ peptides, aggregated on solid-phase microplates, formed Aβ-immunopositive β-sheet-containing structures in the presence of zinc. Formation of these Aβ fibrils was specifically blocked by metal ion chelators. This screening model improves identification of zinc-enhanced Aβ fibrils and anti-Aβ aggregation mediated by zinc chelating. The convenient system could qualitatively and quantitatively assay a large sample pool for Aβ aggregation inhibition and dissolution of Aβ aggregates. This screen is practical, reliable, and versatile for comprehensive detection of amyloid fibrillation and identification of inhibitors of Aβ aggregation. ? 2009 American Chemical Society. |
URI: | 2-s2.0-68849121244 https://scholars.lib.ntu.edu.tw/handle/123456789/569468 |
ISSN: | 32700 | DOI: | 10.1021/ac901011e | SDG/關鍵字: | Alzheimer's; Alzheimer's disease; Clioquinol; High-throughput; Microplates; Screening models; Senile plaques; Side effect; Solid-phase; Zinc chelator; Amines; Chelation; Dissolution; Glycoproteins; Metal ions; Metal recovery; Zinc; amyloid beta protein; beta secretase; clioquinol; zinc; Alzheimer disease; article; beta sheet; chemical structure; morphometrics; screening; solid phase extraction; Amyloid beta-Protein; Chelating Agents; Humans; Models, Theoretical; Peptide Fragments; Recombinant Proteins; Zinc |
顯示於: | 藥學系 |
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