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Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology
BACKGROUND: A growing body of evidence indicates that inflammation is one of the earliest neuropathological events in Alzheimer's disease. Accordingly, we have recently shown the occurrence of an early, pro-inflammatory reaction in the hippocampus of young, three-month-old transgenic McGill-Thy...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352127/ https://www.ncbi.nlm.nih.gov/pubmed/22472085 http://dx.doi.org/10.1186/1742-2094-9-62 |
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author | Ferretti, Maria Teresa Allard, Simon Partridge, Vanessa Ducatenzeiler, Adriana Cuello, A Claudio |
author_facet | Ferretti, Maria Teresa Allard, Simon Partridge, Vanessa Ducatenzeiler, Adriana Cuello, A Claudio |
author_sort | Ferretti, Maria Teresa |
collection | PubMed |
description | BACKGROUND: A growing body of evidence indicates that inflammation is one of the earliest neuropathological events in Alzheimer's disease. Accordingly, we have recently shown the occurrence of an early, pro-inflammatory reaction in the hippocampus of young, three-month-old transgenic McGill-Thy1-APP mice in the absence of amyloid plaques but associated with intracellular accumulation of amyloid beta petide oligomers. The role of such a pro-inflammatory process in the progression of the pathology remained to be elucidated. METHODS AND RESULTS: To clarify this we administered minocycline, a tetracyclic derivative with anti-inflammatory and neuroprotective properties, to young, pre-plaque McGill-Thy1-APP mice for one month. The treatment ended at the age of three months, when the mice were still devoid of plaques. Minocycline treatment corrected the up-regulation of inducible nitric oxide synthase and cyclooxygenase-2 observed in young transgenic placebo mice. Furthermore, the down-regulation of inflammatory markers correlated with a reduction in amyloid precursor protein levels and amyloid precursor protein-related products. Beta-site amyloid precursor protein cleaving enzyme 1 activity and levels were found to be up-regulated in transgenic placebo mice, while minocycline treatment restored these levels to normality. The anti-inflammatory and beta-secretase 1 effects could be partly explained by the inhibition of the nuclear factor kappa B pathway. CONCLUSIONS: Our study suggests that the pharmacological modulation of neuroinflammation might represent a promising approach for preventing or delaying the development of Alzheimer's disease neuropathology at its initial, pre-clinical stages. The results open new vistas to the interplay between inflammation and amyloid pathology. |
format | Online Article Text |
id | pubmed-3352127 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-33521272012-05-16 Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology Ferretti, Maria Teresa Allard, Simon Partridge, Vanessa Ducatenzeiler, Adriana Cuello, A Claudio J Neuroinflammation Research BACKGROUND: A growing body of evidence indicates that inflammation is one of the earliest neuropathological events in Alzheimer's disease. Accordingly, we have recently shown the occurrence of an early, pro-inflammatory reaction in the hippocampus of young, three-month-old transgenic McGill-Thy1-APP mice in the absence of amyloid plaques but associated with intracellular accumulation of amyloid beta petide oligomers. The role of such a pro-inflammatory process in the progression of the pathology remained to be elucidated. METHODS AND RESULTS: To clarify this we administered minocycline, a tetracyclic derivative with anti-inflammatory and neuroprotective properties, to young, pre-plaque McGill-Thy1-APP mice for one month. The treatment ended at the age of three months, when the mice were still devoid of plaques. Minocycline treatment corrected the up-regulation of inducible nitric oxide synthase and cyclooxygenase-2 observed in young transgenic placebo mice. Furthermore, the down-regulation of inflammatory markers correlated with a reduction in amyloid precursor protein levels and amyloid precursor protein-related products. Beta-site amyloid precursor protein cleaving enzyme 1 activity and levels were found to be up-regulated in transgenic placebo mice, while minocycline treatment restored these levels to normality. The anti-inflammatory and beta-secretase 1 effects could be partly explained by the inhibition of the nuclear factor kappa B pathway. CONCLUSIONS: Our study suggests that the pharmacological modulation of neuroinflammation might represent a promising approach for preventing or delaying the development of Alzheimer's disease neuropathology at its initial, pre-clinical stages. The results open new vistas to the interplay between inflammation and amyloid pathology. BioMed Central 2012-04-02 /pmc/articles/PMC3352127/ /pubmed/22472085 http://dx.doi.org/10.1186/1742-2094-9-62 Text en Copyright ©2012 Ferretti et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Ferretti, Maria Teresa Allard, Simon Partridge, Vanessa Ducatenzeiler, Adriana Cuello, A Claudio Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology |
title | Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology |
title_full | Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology |
title_fullStr | Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology |
title_full_unstemmed | Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology |
title_short | Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology |
title_sort | minocycline corrects early, pre-plaque neuroinflammation and inhibits bace-1 in a transgenic model of alzheimer's disease-like amyloid pathology |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352127/ https://www.ncbi.nlm.nih.gov/pubmed/22472085 http://dx.doi.org/10.1186/1742-2094-9-62 |
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