Metallomics for Alzheimer's disease treatment: Use of new generation of chelators combining metal-cation binding and transport properties
Jazyk angličtina Země Francie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
29525434
DOI
10.1016/j.ejmech.2018.02.084
PII: S0223-5234(18)30227-7
Knihovny.cz E-zdroje
- Klíčová slova
- Alzheimer's disease, Amyloid beta, Chelator, Hydrazones, Mechanism of action,
- MeSH
- Alzheimerova nemoc farmakoterapie metabolismus MeSH
- amyloidní beta-protein antagonisté a inhibitory metabolismus MeSH
- chelátory chemická syntéza chemie farmakologie MeSH
- chelátová terapie * MeSH
- cholinesterasové inhibitory chemická syntéza chemie farmakologie MeSH
- kationty chemie farmakologie MeSH
- kovy chemie farmakologie MeSH
- lidé MeSH
- molekulární struktura MeSH
- nádorové buňky kultivované MeSH
- proliferace buněk účinky léků MeSH
- proteinové agregáty účinky léků MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- amyloidní beta-protein MeSH
- chelátory MeSH
- cholinesterasové inhibitory MeSH
- kationty MeSH
- kovy MeSH
- proteinové agregáty 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
Citace poskytuje Crossref.org
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