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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,

. 2018 ; 150 (-) : 140-155. [pub] 20180302

Jazyk angličtina Země Francie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc18024312

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.

Citace poskytuje Crossref.org

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$a D'Acunto, Cosimo Walter $u University of Chemistry and Technology, Technická 5, 16628 Prague 6, Czech Republic.
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$a 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.
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$a Kaplánek, Robert $u University of Chemistry and Technology, Technická 5, 16628 Prague 6, Czech Republic; First Faculty of Medicine-BIOCEV, Charles University, Kateřinská 32, 12108 Prague 2, Czech Republic.
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$a Gbelcová, Helena $u University of Chemistry and Technology, Technická 5, 16628 Prague 6, Czech Republic; Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 81101 Bratislava, Slovakia.
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$a Kejík, Zdeněk $u First Faculty of Medicine-BIOCEV, Charles University, Kateřinská 32, 12108 Prague 2, Czech Republic.
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$a Bříza, Tomáš $u University of Chemistry and Technology, Technická 5, 16628 Prague 6, Czech Republic; First Faculty of Medicine-BIOCEV, Charles University, Kateřinská 32, 12108 Prague 2, Czech Republic.
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$a Vasina, Liudmila $u University of Chemistry and Technology, Technická 5, 16628 Prague 6, Czech Republic; First Faculty of Medicine-BIOCEV, Charles University, Kateřinská 32, 12108 Prague 2, Czech Republic.
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$a Havlík, Martin $u University of Chemistry and Technology, Technická 5, 16628 Prague 6, Czech Republic; First Faculty of Medicine-BIOCEV, Charles University, Kateřinská 32, 12108 Prague 2, Czech Republic.
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$a Ruml, Tomáš $u University of Chemistry and Technology, Technická 5, 16628 Prague 6, Czech Republic. Electronic address: tomas.ruml@vscht.cz.
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$a Král, Vladimír $u University of Chemistry and Technology, Technická 5, 16628 Prague 6, Czech Republic; First Faculty of Medicine-BIOCEV, Charles University, Kateřinská 32, 12108 Prague 2, Czech Republic. Electronic address: vladimir.kral@lf1.cuni.cz.
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