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Oxysterol-binding protein-1 (OSBP1) modulates processing and trafficking of the amyloid precursor protein
BACKGROUND: Evidence from biochemical, epidemiological and genetic findings indicates that cholesterol levels are linked to amyloid-β (Aβ) production and Alzheimer's disease (AD). Oxysterols, which are cholesterol-derived ligands of the liver X receptors (LXRs) and oxysterol binding proteins, s...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323375/ https://www.ncbi.nlm.nih.gov/pubmed/18348724 http://dx.doi.org/10.1186/1750-1326-3-5 |
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author | Zerbinatti, Celina V Cordy, Joanna M Chen, Ci-Di Guillily, Maria Suon, Sokreine Ray, William J Seabrook, Guy R Abraham, Carmela R Wolozin, Benjamin |
author_facet | Zerbinatti, Celina V Cordy, Joanna M Chen, Ci-Di Guillily, Maria Suon, Sokreine Ray, William J Seabrook, Guy R Abraham, Carmela R Wolozin, Benjamin |
author_sort | Zerbinatti, Celina V |
collection | PubMed |
description | BACKGROUND: Evidence from biochemical, epidemiological and genetic findings indicates that cholesterol levels are linked to amyloid-β (Aβ) production and Alzheimer's disease (AD). Oxysterols, which are cholesterol-derived ligands of the liver X receptors (LXRs) and oxysterol binding proteins, strongly regulate the processing of amyloid precursor protein (APP). Although LXRs have been studied extensively, little is known about the biology of oxysterol binding proteins. Oxysterol-binding protein 1 (OSBP1) is a member of a family of sterol-binding proteins with roles in lipid metabolism, regulation of secretory vesicle generation and signal transduction, and it is thought that these proteins may act as sterol sensors to control a variety of sterol-dependent cellular processes. RESULTS: We investigated whether OSBP1 was involved in regulating APP processing and found that overexpression of OSBP1 downregulated the amyloidogenic processing of APP, while OSBP1 knockdown had the opposite effect. In addition, we found that OSBP1 altered the trafficking of APP-Notch2 dimers by causing their accumulation in the Golgi, an effect that could be reversed by treating cells with OSBP1 ligand, 25-hydroxycholesterol. CONCLUSION: These results suggest that OSBP1 could play a role in linking cholesterol metabolism with intracellular APP trafficking and Aβ production, and more importantly indicate that OSBP1 could provide an alternative target for Aβ-directed therapeutic. |
format | Text |
id | pubmed-2323375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-23233752008-04-19 Oxysterol-binding protein-1 (OSBP1) modulates processing and trafficking of the amyloid precursor protein Zerbinatti, Celina V Cordy, Joanna M Chen, Ci-Di Guillily, Maria Suon, Sokreine Ray, William J Seabrook, Guy R Abraham, Carmela R Wolozin, Benjamin Mol Neurodegener Research Article BACKGROUND: Evidence from biochemical, epidemiological and genetic findings indicates that cholesterol levels are linked to amyloid-β (Aβ) production and Alzheimer's disease (AD). Oxysterols, which are cholesterol-derived ligands of the liver X receptors (LXRs) and oxysterol binding proteins, strongly regulate the processing of amyloid precursor protein (APP). Although LXRs have been studied extensively, little is known about the biology of oxysterol binding proteins. Oxysterol-binding protein 1 (OSBP1) is a member of a family of sterol-binding proteins with roles in lipid metabolism, regulation of secretory vesicle generation and signal transduction, and it is thought that these proteins may act as sterol sensors to control a variety of sterol-dependent cellular processes. RESULTS: We investigated whether OSBP1 was involved in regulating APP processing and found that overexpression of OSBP1 downregulated the amyloidogenic processing of APP, while OSBP1 knockdown had the opposite effect. In addition, we found that OSBP1 altered the trafficking of APP-Notch2 dimers by causing their accumulation in the Golgi, an effect that could be reversed by treating cells with OSBP1 ligand, 25-hydroxycholesterol. CONCLUSION: These results suggest that OSBP1 could play a role in linking cholesterol metabolism with intracellular APP trafficking and Aβ production, and more importantly indicate that OSBP1 could provide an alternative target for Aβ-directed therapeutic. BioMed Central 2008-03-18 /pmc/articles/PMC2323375/ /pubmed/18348724 http://dx.doi.org/10.1186/1750-1326-3-5 Text en Copyright © 2008 Zerbinatti 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 Article Zerbinatti, Celina V Cordy, Joanna M Chen, Ci-Di Guillily, Maria Suon, Sokreine Ray, William J Seabrook, Guy R Abraham, Carmela R Wolozin, Benjamin Oxysterol-binding protein-1 (OSBP1) modulates processing and trafficking of the amyloid precursor protein |
title | Oxysterol-binding protein-1 (OSBP1) modulates processing and trafficking of the amyloid precursor protein |
title_full | Oxysterol-binding protein-1 (OSBP1) modulates processing and trafficking of the amyloid precursor protein |
title_fullStr | Oxysterol-binding protein-1 (OSBP1) modulates processing and trafficking of the amyloid precursor protein |
title_full_unstemmed | Oxysterol-binding protein-1 (OSBP1) modulates processing and trafficking of the amyloid precursor protein |
title_short | Oxysterol-binding protein-1 (OSBP1) modulates processing and trafficking of the amyloid precursor protein |
title_sort | oxysterol-binding protein-1 (osbp1) modulates processing and trafficking of the amyloid precursor protein |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323375/ https://www.ncbi.nlm.nih.gov/pubmed/18348724 http://dx.doi.org/10.1186/1750-1326-3-5 |
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