Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ferretti, Maria Teresa, Allard, Simon, Partridge, Vanessa, Ducatenzeiler, Adriana, Cuello, A Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
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
_version_ 1782232852856832000
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
work_keys_str_mv AT ferrettimariateresa minocyclinecorrectsearlypreplaqueneuroinflammationandinhibitsbace1inatransgenicmodelofalzheimersdiseaselikeamyloidpathology
AT allardsimon minocyclinecorrectsearlypreplaqueneuroinflammationandinhibitsbace1inatransgenicmodelofalzheimersdiseaselikeamyloidpathology
AT partridgevanessa minocyclinecorrectsearlypreplaqueneuroinflammationandinhibitsbace1inatransgenicmodelofalzheimersdiseaselikeamyloidpathology
AT ducatenzeileradriana minocyclinecorrectsearlypreplaqueneuroinflammationandinhibitsbace1inatransgenicmodelofalzheimersdiseaselikeamyloidpathology
AT cuelloaclaudio minocyclinecorrectsearlypreplaqueneuroinflammationandinhibitsbace1inatransgenicmodelofalzheimersdiseaselikeamyloidpathology