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Copper Chelator Induced Efficient Episodic Memory Recovery in a Non-Transgenic Alzheimer’s Mouse Model

Alzheimer’s disease (AD) is a neurodegenerative syndrom involving many different biological parameters, including the accumulation of copper metal ions in Aβ amyloid peptides due to a perturbation of copper circulation and homeostasis within the brain. Copper-containing amyloids activated by endogen...

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Autores principales: Ceccom, Johnatan, Coslédan, Frédéric, Halley, Hélène, Francès, Bernard, Lassalle, Jean Michel, Meunier, Bernard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424235/
https://www.ncbi.nlm.nih.gov/pubmed/22927947
http://dx.doi.org/10.1371/journal.pone.0043105
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author Ceccom, Johnatan
Coslédan, Frédéric
Halley, Hélène
Francès, Bernard
Lassalle, Jean Michel
Meunier, Bernard
author_facet Ceccom, Johnatan
Coslédan, Frédéric
Halley, Hélène
Francès, Bernard
Lassalle, Jean Michel
Meunier, Bernard
author_sort Ceccom, Johnatan
collection PubMed
description Alzheimer’s disease (AD) is a neurodegenerative syndrom involving many different biological parameters, including the accumulation of copper metal ions in Aβ amyloid peptides due to a perturbation of copper circulation and homeostasis within the brain. Copper-containing amyloids activated by endogenous reductants are able to generate an oxidative stress that is involved in the toxicity of abnormal amyloids and contribute to the progressive loss of neurons in AD. Since only few drugs are currently available for the treatment of AD, we decided to design small molecules able to interact with copper and we evaluated these drug-candidates with non-transgenic mice, since AD is mainly an aging disease, not related to genetic disorders. We created a memory deficit mouse model by a single icv injection of Aβ(1–42) peptide, in order to mimic the early stage of the disease and the key role of amyloid oligomers in AD. No memory deficit was observed in the control mice with the antisense Aβ(42-1) peptide. Here we report the capacity of a new copper-specific chelating agent, a bis-8-aminoquinoline PA1637, to fully reverse the deficit of episodic memory after three weeks of treatment by oral route on non-transgenic amyloid-impaired mice. Clioquinol and memantine have been used as comparators to validate this fast and efficient mouse model.
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spelling pubmed-34242352012-08-27 Copper Chelator Induced Efficient Episodic Memory Recovery in a Non-Transgenic Alzheimer’s Mouse Model Ceccom, Johnatan Coslédan, Frédéric Halley, Hélène Francès, Bernard Lassalle, Jean Michel Meunier, Bernard PLoS One Research Article Alzheimer’s disease (AD) is a neurodegenerative syndrom involving many different biological parameters, including the accumulation of copper metal ions in Aβ amyloid peptides due to a perturbation of copper circulation and homeostasis within the brain. Copper-containing amyloids activated by endogenous reductants are able to generate an oxidative stress that is involved in the toxicity of abnormal amyloids and contribute to the progressive loss of neurons in AD. Since only few drugs are currently available for the treatment of AD, we decided to design small molecules able to interact with copper and we evaluated these drug-candidates with non-transgenic mice, since AD is mainly an aging disease, not related to genetic disorders. We created a memory deficit mouse model by a single icv injection of Aβ(1–42) peptide, in order to mimic the early stage of the disease and the key role of amyloid oligomers in AD. No memory deficit was observed in the control mice with the antisense Aβ(42-1) peptide. Here we report the capacity of a new copper-specific chelating agent, a bis-8-aminoquinoline PA1637, to fully reverse the deficit of episodic memory after three weeks of treatment by oral route on non-transgenic amyloid-impaired mice. Clioquinol and memantine have been used as comparators to validate this fast and efficient mouse model. Public Library of Science 2012-08-21 /pmc/articles/PMC3424235/ /pubmed/22927947 http://dx.doi.org/10.1371/journal.pone.0043105 Text en © 2012 Ceccom et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ceccom, Johnatan
Coslédan, Frédéric
Halley, Hélène
Francès, Bernard
Lassalle, Jean Michel
Meunier, Bernard
Copper Chelator Induced Efficient Episodic Memory Recovery in a Non-Transgenic Alzheimer’s Mouse Model
title Copper Chelator Induced Efficient Episodic Memory Recovery in a Non-Transgenic Alzheimer’s Mouse Model
title_full Copper Chelator Induced Efficient Episodic Memory Recovery in a Non-Transgenic Alzheimer’s Mouse Model
title_fullStr Copper Chelator Induced Efficient Episodic Memory Recovery in a Non-Transgenic Alzheimer’s Mouse Model
title_full_unstemmed Copper Chelator Induced Efficient Episodic Memory Recovery in a Non-Transgenic Alzheimer’s Mouse Model
title_short Copper Chelator Induced Efficient Episodic Memory Recovery in a Non-Transgenic Alzheimer’s Mouse Model
title_sort copper chelator induced efficient episodic memory recovery in a non-transgenic alzheimer’s mouse model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424235/
https://www.ncbi.nlm.nih.gov/pubmed/22927947
http://dx.doi.org/10.1371/journal.pone.0043105
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