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Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on β-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells
BACKGROUND: Activation of the liver × receptors (LXRs) by exogenous ligands stimulates the degradation of β-amyloid 1–42 (Aβ42), a peptide that plays a central role in the pathogenesis of Alzheimer's disease (AD). The oxidized cholesterol products (oxysterols), 24-hydroxycholesterol (24-OHC) an...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654562/ https://www.ncbi.nlm.nih.gov/pubmed/19126211 http://dx.doi.org/10.1186/1750-1326-4-1 |
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author | Prasanthi, Jaya RP Huls, Amber Thomasson, Sarah Thompson, Alex Schommer, Eric Ghribi, Othman |
author_facet | Prasanthi, Jaya RP Huls, Amber Thomasson, Sarah Thompson, Alex Schommer, Eric Ghribi, Othman |
author_sort | Prasanthi, Jaya RP |
collection | PubMed |
description | BACKGROUND: Activation of the liver × receptors (LXRs) by exogenous ligands stimulates the degradation of β-amyloid 1–42 (Aβ42), a peptide that plays a central role in the pathogenesis of Alzheimer's disease (AD). The oxidized cholesterol products (oxysterols), 24-hydroxycholesterol (24-OHC) and 27-hydroxycholesterol (27-OHC), are endogenous activators of LXRs. However, the mechanisms by which these oxysterols may modulate Aβ42 levels are not well known. RESULTS: We determined the effect of 24-OHC and/or 27-OHC on Aβ generation in SH-SY5Y cells. We found that while 27-OHC increases levels of Aβ42, 24-OHC did not affect levels of this peptide. Increased Aβ42 levels with 27-OHC are associated with increased levels of β-amyloid precursor protein (APP) as well as β-secretase (BACE1), the enzyme that cleaves APP to yield Aβ. Unchanged Aβ42 levels with 24-OHC are associated with increased levels of sAPPα, suggesting that 24-OHC favors the processing of APP to the non-amyloidogenic pathway. Interestingly, 24-OHC, but not 27-OHC, increases levels of the ATP-binding cassette transporters, ABCA1 and ABCG1, which regulate cholesterol transport within and between cells. CONCLUSION: These results suggest that cholesterol metabolites are linked to Aβ42 production. 24-OHC may favor the non-amyloidogenic pathway and 27-OHC may enhance production of Aβ42 by upregulating APP and BACE1. Regulation of 24-OHC: 27-OHC ratio could be an important strategy in controlling Aβ42 levels in AD. |
format | Text |
id | pubmed-2654562 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-26545622009-03-13 Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on β-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells Prasanthi, Jaya RP Huls, Amber Thomasson, Sarah Thompson, Alex Schommer, Eric Ghribi, Othman Mol Neurodegener Research Article BACKGROUND: Activation of the liver × receptors (LXRs) by exogenous ligands stimulates the degradation of β-amyloid 1–42 (Aβ42), a peptide that plays a central role in the pathogenesis of Alzheimer's disease (AD). The oxidized cholesterol products (oxysterols), 24-hydroxycholesterol (24-OHC) and 27-hydroxycholesterol (27-OHC), are endogenous activators of LXRs. However, the mechanisms by which these oxysterols may modulate Aβ42 levels are not well known. RESULTS: We determined the effect of 24-OHC and/or 27-OHC on Aβ generation in SH-SY5Y cells. We found that while 27-OHC increases levels of Aβ42, 24-OHC did not affect levels of this peptide. Increased Aβ42 levels with 27-OHC are associated with increased levels of β-amyloid precursor protein (APP) as well as β-secretase (BACE1), the enzyme that cleaves APP to yield Aβ. Unchanged Aβ42 levels with 24-OHC are associated with increased levels of sAPPα, suggesting that 24-OHC favors the processing of APP to the non-amyloidogenic pathway. Interestingly, 24-OHC, but not 27-OHC, increases levels of the ATP-binding cassette transporters, ABCA1 and ABCG1, which regulate cholesterol transport within and between cells. CONCLUSION: These results suggest that cholesterol metabolites are linked to Aβ42 production. 24-OHC may favor the non-amyloidogenic pathway and 27-OHC may enhance production of Aβ42 by upregulating APP and BACE1. Regulation of 24-OHC: 27-OHC ratio could be an important strategy in controlling Aβ42 levels in AD. BioMed Central 2009-01-06 /pmc/articles/PMC2654562/ /pubmed/19126211 http://dx.doi.org/10.1186/1750-1326-4-1 Text en Copyright © 2009 Prasanthi 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 Prasanthi, Jaya RP Huls, Amber Thomasson, Sarah Thompson, Alex Schommer, Eric Ghribi, Othman Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on β-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells |
title | Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on β-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells |
title_full | Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on β-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells |
title_fullStr | Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on β-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells |
title_full_unstemmed | Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on β-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells |
title_short | Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on β-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells |
title_sort | differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on β-amyloid precursor protein levels and processing in human neuroblastoma sh-sy5y cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654562/ https://www.ncbi.nlm.nih.gov/pubmed/19126211 http://dx.doi.org/10.1186/1750-1326-4-1 |
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