NDLI: Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on β-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells

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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

Content Provider	Springer Nature : BioMed Central
Author	Prasanthi, Jaya RP Huls, Amber Thomasson, Sarah Thompson, Alex Schommer, Eric Ghribi, Othman
Abstract	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.
Related Links	https://molecularneurodegeneration.biomedcentral.com/counter/pdf/10.1186/1750-1326-4-1.pdf
Ending Page	8
Page Count	8
Starting Page	1
File Format	HTM / HTML
ISSN	17501326
DOI	10.1186/1750-1326-4-1
Journal	Molecular Neurodegeneration
Issue Number	1
Volume Number	4
Language	English
Publisher	BioMed Central
Publisher Date	2009-01-06
Access Restriction	Open
Subject Keyword	Neurosciences Neurology Molecular Medicine ABCG1 Expression Amyloidogenic Pathway BACE1 Level High Blood Cholesterol Level ABCA1 Level
Content Type	Text
Resource Type	Article
Subject	Neurology (clinical) Molecular Biology Cellular and Molecular Neuroscience
Journal Impact Factor	15.1/2023
5-Year Journal Impact Factor	16.8/2023

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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

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