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MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice

Hawkes, C. A.; Shaw, J. E.; Brown, M.; Sampson, A. P.; McLaurin, J. and Carare, R. O. (2013). MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice. Neurodegenerative Diseases, 13(1) pp. 17–23.

DOI (Digital Object Identifier) Link: https://doi.org/10.1159/000351096
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Abstract

Background: Deposition of amyloid-β (Aβ) in blood vessel walls as cerebral amyloid angiopathy (CAA) is observed in the majority of Alzheimer's disease (AD) brains. Inhibition of the 5-lipoxygenase (5-LOX) pathway has recently been suggested to play a role in reducing parenchymal Aβ deposition. However, products of the 5-LOX pathway also activate the peroxisome proliferator-activated receptor (PPAR) family, which promotes clearance of Aβ from the brain.
Methods: In the present study, we investigated the effect of MK886, a 5-LOX-activating protein (FLAP) inhibitor and PPARα antagonist, on CAA severity in TgCRND8 mice overexpressing the human Swedish and Indiana amyloid precursor protein mutations.
Results: We found that MK886 significantly reduced brain levels of nicastrin and PPARα, but did not affect levels of β-secretase, apolipoprotein E or low-density lipoprotein receptor-related protein-1. CAA severity and parenchymal plaque load was significantly decreased in both the cortex and hippocampus of mice treated with MK886 compared to control mice.
Conclusion: These data suggest that 5-LOX and FLAP inhibitors may be useful in the treatment of CAA and AD.

Item Type: Journal Item
Copyright Holders: 2013 S. Karger AG,
Extra Information: leukotriene inhibitor; cerebral amyloid angiopathy; peroxisome proliferator-activated receptor
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
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Item ID: 44085
Depositing User: Cheryl Hawkes
Date Deposited: 10 Sep 2015 09:07
Last Modified: 07 Dec 2018 10:34
URI: http://oro.open.ac.uk/id/eprint/44085
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