A prochelator activated by beta-secretase inhibits Abeta aggregation and suppresses copper-induced reactive oxygen species formation.
Data(s) |
14/04/2010
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Formato |
4994 - 4995 |
Identificador |
http://www.ncbi.nlm.nih.gov/pubmed/20297791 J Am Chem Soc, 2010, 132 (14), pp. 4994 - 4995 http://hdl.handle.net/10161/4038 1520-5126 |
Idioma(s) |
ENG en_US |
Relação |
J Am Chem Soc 10.1021/ja100943r Journal of the American Chemical Society |
Tipo |
Journal Article |
Cobertura |
United States |
Resumo |
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. |
Palavras-Chave | #Amyloid Precursor Protein Secretases #Amyloid beta-Peptides #Chelating Agents #Copper #Organometallic Compounds #Reactive Oxygen Species #Structure-Activity Relationship |