Therapeutic implications of the prostaglandin pathway in Alzheimer's disease.
Therapeutic implications of the prostaglandin pathway in Alzheimer's disease.
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DOI：
10.1016/j.bcp.2013.12.014
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发表时间：
2014-04-15
影响因子：
5.8
通讯作者：
Keene, C. Dirk
中科院分区：
文献类型：
--
作者：
Cudaback, Eiron;Jorstad, Nikolas L.;Yang, Yue;Montine, Thomas J.;Keene, C. Dirk
An important pathologic hallmark of Alzheimer’s disease (AD) is neuroinflammation, a process characterized in AD by disproportionate activation of cells (microglia and astrocytes, primarily) of the non-specific innate immune system within the CNS. While inflammation itself is not intrinsically detrimental, a delicate balance of pro- and anti-inflammatory signals must be maintained to ensure that long-term exaggerated responses do not damage the brain over time. Non-steroidal anti-inflammatory drugs (NSAIDs) represent a broad class of powerful therapeutics that temper inflammation by inhibiting cyclooxygenase-mediated signaling pathways including prostaglandins, which are the principal mediators of CNS neuroinflammation. While historically used to treat discrete or systemic inflammatory conditions, epidemiologic evidence suggests that protracted NSAID use may delay AD onset, as well as decrease disease severity and rate of progression. Unfortunately, clinical trials with NSAIDs have thus far yielded disappointing results, including premature discontinuation of a large-scale prevention trial due to unexpected cardiovascular side effects. Here we review the literature and make the argument that more targeted exploitation of downstream prostaglandin signaling pathways may offer significant therapeutic benefits for AD while minimizing adverse side effects. Directed strategies such as these may ultimately help to delay the deleterious consequences of brain aging and might someday lead to new therapies for AD and other chronic neurodegenerative diseases.
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影响因子：
3.6
作者：
Cimino, Patrick J.;Yang, Yue;Li, Xianwu;Hemingway, Jake F.;Cherne, Makenzie K.;Khademi, Shawn B.;Fukui, Yoshinori;Montine, Kathleen S.;Montine, Thomas J.;Keene, C. Dirk
通讯作者：
Keene, C. Dirk
DOI：
10.1038/jcbfm.2008.88
发表时间：
2009-01
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
--
DOI：
10.18632/aging.100021
发表时间：
2009-02-11
期刊：
Aging
影响因子：
--
作者：
Choi SH;Bosetti F
通讯作者：
Bosetti F
影响因子：
3.3
作者：
Ahmad, Muzamil;Ahmad, Abdullah Shafique;Dore, Sylvain
通讯作者：
Dore, Sylvain
DOI：
10.1016/j.jalz.2010.12.014
发表时间：
2011-07
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Breitner JC;Baker LD;Montine TJ;Meinert CL;Lyketsos CG;Ashe KH;Brandt J;Craft S;Evans DE;Green RC;Ismail MS;Martin BK;Mullan MJ;Sabbagh M;Tariot PN;ADAPT Research Group
通讯作者：
ADAPT Research Group