An improved screening model to identify inhibitors targeting zinc-enhanced amyloid aggregation

Pei Teh Chang, Fan Lu Kung, Rahul Subhash Talekar, Chien Shu Chen, Shin Yu Lai, Hsueh Yun Lee, Ji Wang Chern

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6944-6951
Number of pages8
JournalAnalytical Chemistry
Volume81
Issue number16
DOIs
Publication statusPublished - Aug 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry

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  • Cite this

    Chang, P. T., Kung, F. L., Talekar, R. S., Chen, C. S., Lai, S. Y., Lee, H. Y., & Chern, J. W. (2009). An improved screening model to identify inhibitors targeting zinc-enhanced amyloid aggregation. Analytical Chemistry, 81(16), 6944-6951. https://doi.org/10.1021/ac901011e