| 44085 |
Creator |
d64a4c8b9d6fb32d441f1cd9c453d93b |
| 44085 |
Creator |
ext-29a776867d13639ffc6ba16f6d5709e4 |
| 44085 |
Creator |
ext-d64ce70913a95c8aea0f6d13a9267337 |
| 44085 |
Creator |
ext-bb0eebbfe72de5a7c025332f47d5ba64 |
| 44085 |
Creator |
ext-0b71dcf412e1dbab4cdd3227c011e978 |
| 44085 |
Creator |
ext-9233bc8e92fe30ee2e3f241fa02c1d37 |
| 44085 |
Date |
2013-12 |
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Is Part Of |
repository |
| 44085 |
Is Part Of |
pc0c799671d25f857117d71ba0ecc2032 |
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abstract |
<b>Background:</b> 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. <br></br><b>Methods:</b> 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. <br></br><b>Results:</b> 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.
<br></br><b>Conclusion:</b> These data suggest that 5-LOX and FLAP inhibitors may
be useful in the treatment of CAA and AD. |
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authorList |
authors |
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issue |
1 |
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status |
peerReviewed |
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volume |
13 |
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type |
AcademicArticle |
| 44085 |
type |
Article |
| 44085 |
label |
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. |
| 44085 |
label |
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. |
| 44085 |
Title |
MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice |
| 44085 |
in dataset |
oro |