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Metallomics for Alzheimer's disease treatment: Use of new generation of chelators combining metal-cation binding and transport properties
CW. D'Acunto, R. Kaplánek, H. Gbelcová, Z. Kejík, T. Bříza, L. Vasina, M. Havlík, T. Ruml, V. Král,
Language English Country France
Document type Journal Article
- MeSH
- Alzheimer Disease drug therapy metabolism MeSH
- Amyloid beta-Peptides antagonists & inhibitors metabolism MeSH
- Chelating Agents chemical synthesis chemistry pharmacology MeSH
- Chelation Therapy * MeSH
- Cholinesterase Inhibitors chemical synthesis chemistry pharmacology MeSH
- Cations chemistry pharmacology MeSH
- Metals chemistry pharmacology MeSH
- Humans MeSH
- Molecular Structure MeSH
- Tumor Cells, Cultured MeSH
- Cell Proliferation drug effects MeSH
- Protein Aggregates drug effects MeSH
- Cell Survival drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting tens of million people. Currently marketed drugs have limited therapeutic efficacy and only slowing down the neurodegenerative process. Interestingly, it has been suggested that biometal cations in the amyloid beta (Aβ) aggregate deposits contribute to neurotoxicity and degenerative changes in AD. Thus, chelation therapy could represent novel mode of therapeutic intervention. Here we describe the features of chelators with therapeutically relevant mechanism of action. We have found that the tested compounds effectively reduce the toxicity of exogenous Aβ and suppress its endogenous production as well as decrease oxidative stress. Cholyl hydrazones were found to be the most active compounds. In summary, our data show that cation complexation, together with improving transport efficacy may represent basis for eventual treatment strategy in AD.
1st Faculty of Medicine BIOCEV Charles University Kateřinská 32 12108 Prague 2 Czech Republic
University of Chemistry and Technology Technická 5 16628 Prague 6 Czech Republic
References provided by Crossref.org
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