A prochelator activated by beta-secretase inhibits Abeta aggregation and suppresses copper-induced reactive oxygen species formation.
Abstract
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.
Type
Journal articleSubject
Amyloid Precursor Protein SecretasesAmyloid beta-Peptides
Chelating Agents
Copper
Organometallic Compounds
Reactive Oxygen Species
Structure-Activity Relationship
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https://hdl.handle.net/10161/4038Published Version (Please cite this version)
10.1021/ja100943rPublication Info
Folk, Drew S; & Franz, Katherine J (2010). A prochelator activated by beta-secretase inhibits Abeta aggregation and suppresses
copper-induced reactive oxygen species formation. J Am Chem Soc, 132(14). pp. 4994-4995. 10.1021/ja100943r. Retrieved from https://hdl.handle.net/10161/4038.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Katherine J. Franz
Chair of the Department of Chemistry
Research in the Franz group is involved in elucidating the structural and functional
consequences of metal ion coordination in biological systems. We are particularly
interested in understanding the coordination chemistry utilized by biology to manage
essential yet toxic species like copper and iron. Understanding these principles
further guides our development of new chemical tools to manipulate biological metal
ion location, speciation, and reactivity for potential therapeutic benefit. We use

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