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CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease
Alzheimer's disease (AD) is characterized by neuronal atrophy caused by soluble amyloid β protein (Aβ) peptide “oligomers” and a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. We show that CNI-1493, a tetravalent guanylhydrazone with established...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442637/ https://www.ncbi.nlm.nih.gov/pubmed/18573905 http://dx.doi.org/10.1084/jem.20060467 |
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author | Bacher, Michael Dodel, Richard Aljabari, Bayan Keyvani, Kathy Marambaud, Philippe Kayed, Rakez Glabe, Charles Goertz, Nicole Hoppmann, Anne Sachser, Norbert Klotsche, Jens Schnell, Susanne Lewejohann, Lars Al-Abed, Yousef |
author_facet | Bacher, Michael Dodel, Richard Aljabari, Bayan Keyvani, Kathy Marambaud, Philippe Kayed, Rakez Glabe, Charles Goertz, Nicole Hoppmann, Anne Sachser, Norbert Klotsche, Jens Schnell, Susanne Lewejohann, Lars Al-Abed, Yousef |
author_sort | Bacher, Michael |
collection | PubMed |
description | Alzheimer's disease (AD) is characterized by neuronal atrophy caused by soluble amyloid β protein (Aβ) peptide “oligomers” and a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. We show that CNI-1493, a tetravalent guanylhydrazone with established antiinflammatory properties, interferes with Aβ assembly and protects neuronal cells from the toxic effect of soluble Aβ oligomers. Administration of CNI-1493 to TgCRND8 mice overexpressing human amyloid precursor protein (APP) for a treatment period of 8 wk significantly reduced Aβ deposition. CNI-1493 treatment resulted in 70% reduction of amyloid plaque area in the cortex and 87% reduction in the hippocampus of these animals. Administration of CNI-1493 significantly improved memory performance in a cognition task compared with vehicle-treated mice. In vitro analysis of CNI-1493 on APP processing in an APP-overexpressing cell line revealed a significant dose-dependent decrease of total Aβ accumulation. This study indicates that the antiinflammatory agent CNI-1493 can ameliorate the pathophysiology and cognitive defects in a murine model of AD. |
format | Text |
id | pubmed-2442637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-24426372009-01-07 CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease Bacher, Michael Dodel, Richard Aljabari, Bayan Keyvani, Kathy Marambaud, Philippe Kayed, Rakez Glabe, Charles Goertz, Nicole Hoppmann, Anne Sachser, Norbert Klotsche, Jens Schnell, Susanne Lewejohann, Lars Al-Abed, Yousef J Exp Med Brief Definitive Reports Alzheimer's disease (AD) is characterized by neuronal atrophy caused by soluble amyloid β protein (Aβ) peptide “oligomers” and a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. We show that CNI-1493, a tetravalent guanylhydrazone with established antiinflammatory properties, interferes with Aβ assembly and protects neuronal cells from the toxic effect of soluble Aβ oligomers. Administration of CNI-1493 to TgCRND8 mice overexpressing human amyloid precursor protein (APP) for a treatment period of 8 wk significantly reduced Aβ deposition. CNI-1493 treatment resulted in 70% reduction of amyloid plaque area in the cortex and 87% reduction in the hippocampus of these animals. Administration of CNI-1493 significantly improved memory performance in a cognition task compared with vehicle-treated mice. In vitro analysis of CNI-1493 on APP processing in an APP-overexpressing cell line revealed a significant dose-dependent decrease of total Aβ accumulation. This study indicates that the antiinflammatory agent CNI-1493 can ameliorate the pathophysiology and cognitive defects in a murine model of AD. The Rockefeller University Press 2008-07-07 /pmc/articles/PMC2442637/ /pubmed/18573905 http://dx.doi.org/10.1084/jem.20060467 Text en © 2008 Bacher et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Reports Bacher, Michael Dodel, Richard Aljabari, Bayan Keyvani, Kathy Marambaud, Philippe Kayed, Rakez Glabe, Charles Goertz, Nicole Hoppmann, Anne Sachser, Norbert Klotsche, Jens Schnell, Susanne Lewejohann, Lars Al-Abed, Yousef CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease |
title | CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease |
title_full | CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease |
title_fullStr | CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease |
title_full_unstemmed | CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease |
title_short | CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease |
title_sort | cni-1493 inhibits aβ production, plaque formation, and cognitive deterioration in an animal model of alzheimer's disease |
topic | Brief Definitive Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442637/ https://www.ncbi.nlm.nih.gov/pubmed/18573905 http://dx.doi.org/10.1084/jem.20060467 |
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