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COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo
Collagen XXV alpha 1 (COL25A1) is a collagenous type II transmembrane protein purified from senile plaques of Alzheimer’s disease (AD) brains. COL25A1 alleles have been associated with increased risk for AD in a Swedish population. COL25A1 is specifically expressed in neurons and binds to aggregated...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Springer-Verlag
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807601/ https://www.ncbi.nlm.nih.gov/pubmed/19548013 http://dx.doi.org/10.1007/s10048-009-0201-5 |
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author | Tong, Ying Xu, Ying Scearce-Levie, Kimberly Ptáček, Louis J. Fu, Ying-Hui |
author_facet | Tong, Ying Xu, Ying Scearce-Levie, Kimberly Ptáček, Louis J. Fu, Ying-Hui |
author_sort | Tong, Ying |
collection | PubMed |
description | Collagen XXV alpha 1 (COL25A1) is a collagenous type II transmembrane protein purified from senile plaques of Alzheimer’s disease (AD) brains. COL25A1 alleles have been associated with increased risk for AD in a Swedish population. COL25A1 is specifically expressed in neurons and binds to aggregated Aβ in vitro. However, its contribution to the pathogenesis of AD and in vivo function are unknown. Here, we report that over-expression of COL25A1 in transgenic mice increases p35/p25 and β-site APP-cleaving enzyme 1 (BACE1) levels, facilitates intracellular aggregation and extracellular matrix deposits of Aβ, and causes synaptophysin loss and astrocyte activation. COL25A1 mice displayed reduced anxiety-like behavior in elevated plus maze and open field tests and significantly slower swimming speed in Morris water maze. In stable cell lines, motifs in noncollagenous domains of COL25A1 were important for the induction of BACE1 expression. These findings demonstrate that COL25A1 leads to AD-like pathology in vivo. Modulation of COL25A1 function may represent an alternative therapeutic intervention for AD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10048-009-0201-5) contains supplementary material, which is available to authorized users. |
format | Text |
id | pubmed-2807601 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-28076012010-01-22 COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo Tong, Ying Xu, Ying Scearce-Levie, Kimberly Ptáček, Louis J. Fu, Ying-Hui Neurogenetics Original Article Collagen XXV alpha 1 (COL25A1) is a collagenous type II transmembrane protein purified from senile plaques of Alzheimer’s disease (AD) brains. COL25A1 alleles have been associated with increased risk for AD in a Swedish population. COL25A1 is specifically expressed in neurons and binds to aggregated Aβ in vitro. However, its contribution to the pathogenesis of AD and in vivo function are unknown. Here, we report that over-expression of COL25A1 in transgenic mice increases p35/p25 and β-site APP-cleaving enzyme 1 (BACE1) levels, facilitates intracellular aggregation and extracellular matrix deposits of Aβ, and causes synaptophysin loss and astrocyte activation. COL25A1 mice displayed reduced anxiety-like behavior in elevated plus maze and open field tests and significantly slower swimming speed in Morris water maze. In stable cell lines, motifs in noncollagenous domains of COL25A1 were important for the induction of BACE1 expression. These findings demonstrate that COL25A1 leads to AD-like pathology in vivo. Modulation of COL25A1 function may represent an alternative therapeutic intervention for AD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10048-009-0201-5) contains supplementary material, which is available to authorized users. Springer-Verlag 2009-06-23 2010 /pmc/articles/PMC2807601/ /pubmed/19548013 http://dx.doi.org/10.1007/s10048-009-0201-5 Text en © The Author(s) 2009 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Original Article Tong, Ying Xu, Ying Scearce-Levie, Kimberly Ptáček, Louis J. Fu, Ying-Hui COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo |
title | COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo |
title_full | COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo |
title_fullStr | COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo |
title_full_unstemmed | COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo |
title_short | COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo |
title_sort | col25a1 triggers and promotes alzheimer’s disease-like pathology in vivo |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807601/ https://www.ncbi.nlm.nih.gov/pubmed/19548013 http://dx.doi.org/10.1007/s10048-009-0201-5 |
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