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A prochelator activated by beta-secretase inhibits Abeta aggregation and suppresses copper-induced reactive oxygen species formation.

Publication ,  Journal Article
Folk, DS; Franz, KJ
Published in: Journal of the American Chemical Society
April 2010

The intersection of the amyloid cascade hypothesis and the implication of metal ions in Alzheimer's disease progression has sparked an interest in using metal-binding compounds as potential therapeutic agents. In the present work, we describe a prochelator SWH that is enzymatically activated by beta-secretase to produce a high affinity copper chelator CP. Because beta-secretase is responsible for the amyloidogenic processing of the amyloid precursor protein, this prochelator strategy imparts disease specificity toward copper chelation not possible with general metal chelators. Furthermore, once activated, CP efficiently sequesters copper from amyloid-beta, prevents and disassembles copper-induced amyloid-beta aggregation, and diminishes copper-promoted reactive oxygen species formation.

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Published In

Journal of the American Chemical Society

DOI

EISSN

1520-5126

ISSN

0002-7863

Publication Date

April 2010

Volume

132

Issue

14

Start / End Page

4994 / 4995

Related Subject Headings

  • Structure-Activity Relationship
  • Reactive Oxygen Species
  • Organometallic Compounds
  • General Chemistry
  • Copper
  • Chelating Agents
  • Amyloid beta-Peptides
  • Amyloid Precursor Protein Secretases
  • 40 Engineering
  • 34 Chemical sciences
 

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Folk, D. S., & Franz, K. J. (2010). A prochelator activated by beta-secretase inhibits Abeta aggregation and suppresses copper-induced reactive oxygen species formation. Journal of the American Chemical Society, 132(14), 4994–4995. https://doi.org/10.1021/ja100943r
Folk, Drew S., and Katherine J. Franz. “A prochelator activated by beta-secretase inhibits Abeta aggregation and suppresses copper-induced reactive oxygen species formation.Journal of the American Chemical Society 132, no. 14 (April 2010): 4994–95. https://doi.org/10.1021/ja100943r.
Folk, Drew S., and Katherine J. Franz. “A prochelator activated by beta-secretase inhibits Abeta aggregation and suppresses copper-induced reactive oxygen species formation.Journal of the American Chemical Society, vol. 132, no. 14, Apr. 2010, pp. 4994–95. Epmc, doi:10.1021/ja100943r.
Folk DS, Franz KJ. A prochelator activated by beta-secretase inhibits Abeta aggregation and suppresses copper-induced reactive oxygen species formation. Journal of the American Chemical Society. 2010 Apr;132(14):4994–4995.
Journal cover image

Published In

Journal of the American Chemical Society

DOI

EISSN

1520-5126

ISSN

0002-7863

Publication Date

April 2010

Volume

132

Issue

14

Start / End Page

4994 / 4995

Related Subject Headings

  • Structure-Activity Relationship
  • Reactive Oxygen Species
  • Organometallic Compounds
  • General Chemistry
  • Copper
  • Chelating Agents
  • Amyloid beta-Peptides
  • Amyloid Precursor Protein Secretases
  • 40 Engineering
  • 34 Chemical sciences