Lipid peroxidation up-regulates BACE1 expression in vivo: a possible early event of amyloidogenesis in Alzheimer's disease.
Lipid peroxidation up-regulates BACE1 expression in vivo: a possible early event of amyloidogenesis in Alzheimer's disease.
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DOI：
10.1111/j.1471-4159.2008.05603.x
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发表时间：
2008-10
影响因子：
4.7
通讯作者：
Ran Q
中科院分区：
文献类型：
--
作者：
Chen L;Na R;Gu M;Richardson A;Ran Q
Increased lipid peroxidation is shown to be an early event of AD. However, it is not clear whether and how increased lipid peroxidation might lead to amyloidogenesis, a hallmark of AD. Gpx4 is an essential antioxidant defense enzyme that protects an organism against lipid peroxidation. Gpx4+/- mice show increased lipid peroxidation in brain, as evidenced by their elevated levels of 4-HNE. To understand the role of lipid peroxidation in amyloidogenesis, we studied secretase activities in Gpx4+/- mice as a function of age. Both young (6-month) and middle-aged (17- to 20- month) Gpx4+/- mice had higher levels of β-secretase activity than their age-matched wildtype controls, and the increased β-secretase activity in Gpx4+/- mice was a result of upregulation of BACE1 expression at the protein level. The high level of BACE1 protein led to increased endogenous Aβ1-40 in middle-aged Gpx4+/- mice. We further studied amyloidogenesis in APPGpx4+/- mice. Our data indicate that APPGpx4+/- mice had significantly increased amyloid plaque burdens and increased Aβ1-40 and Aβ1-42 levels compared to APPGpx4+/+ mice. Therefore, our results indicate that increased lipid peroxidation leads to increased amyloidogenesis through upregulation of BACE1 expression in vivo, a mechanism that may be important in pathogenesis of AD at early stages.
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DOI：
10.1083/jcb.200207113
发表时间：
2003-01-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ehehalt R;Keller P;Haass C;Thiele C;Simons K
通讯作者：
Simons K
影响因子：
2.5
作者：
Butterfield, DA;Reed, T;Sultana, R
通讯作者：
Sultana, R
影响因子：
4.8
作者：
Bennett, BD;Denis, P;Vassar, R
通讯作者：
Vassar, R
影响因子：
4.8
作者：
Lenz, G;Avruch, J
通讯作者：
Avruch, J
影响因子：
7.4
作者：
PARK, JW;FLOYD, RA
通讯作者：
FLOYD, RA