Triflusal reduces dense-core plaque load, associated axonal alterations and inflammatory changes, and rescues cognition in a transgenic mouse model of Alzheimer's disease.
Triflusal reduces dense-core plaque load, associated axonal alterations and inflammatory changes, and rescues cognition in a transgenic mouse model of Alzheimer's disease.
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DOI：
10.1016/j.nbd.2010.01.019
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发表时间：
2010-06
影响因子：
6.1
通讯作者：
Gómez-Isla T
中科院分区：
文献类型：
--
作者：
Coma M;Serenó L;Da Rocha-Souto B;Scotton TC;España J;Sánchez MB;Rodríguez M;Agulló J;Guardia-Laguarta C;Garcia-Alloza M;Borrelli LA;Clarimón J;Lleó A;Bacskai BJ;Saura CA;Hyman BT;Gómez-Isla T
炎症与阿尔茨海默病（AD）脑中的两种典型病变（淀粉样蛋白沉积和神经元缠结）相关。最近的数据表明，Triflusal是一种在体内中枢神经系统中具有强效抗炎作用的化合物，可能会延迟从遗忘性轻度认知障碍到完全确定的痴呆临床表现的转换。在本研究中，我们研究了三氟柳对AD转基因小鼠模型（Tg 2576）脑Aβ蓄积、神经炎症、轴突弯曲和认知的影响。三氟柳治疗未改变总脑Aβ蓄积，但显著降低了致密核心斑块负荷和相关胶质细胞增殖、促炎细胞因子水平和异常轴突弯曲，并挽救了Tg 2576小鼠的认知缺陷。行为的好处被发现涉及增加表达的c-fos和BDNF，CREB调控的两个基因，作为信号转导级联的一部分，潜在的分子基础的长时程增强。这些结果增加了Triflusal在AD中潜在有益作用的临床前证据。
Inflammation has been associated with the two classic lesions in the Alzheimer’s (AD) brain, amyloid deposits and neurofibrillary tangles. Recent data suggest that Triflusal, a compound with potent anti-inflammatory effects in the central nervous system in vivo, might delay the conversion from amnestic mild cognitive impairment to a fully established clinical picture of dementia. In the present study, we investigated the effect of Triflusal on brain Aβ accumulation, neuroinflammation, axonal curvature and cognition in an AD transgenic mouse model (Tg2576). Triflusal treatment did not alter the total brain Aβ accumulation but significantly reduced dense-cored plaque load and associated glial cell proliferation, proinflammatory cytokine levels and abnormal axonal curvature, and rescued cognitive deficits in Tg2576 mice. Behavioral benefit was found to involve increased expression of c-fos and BDNF, two of the genes regulated by CREB, as part of the signal transduction cascade underlying the molecular basis of long-term potentiation. These results add preclinical evidence of a potentially beneficial effect of Triflusal in AD.
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DOI：
10.1093/jnen/62.2.137
发表时间：
2003-02-01
影响因子：
3.2
作者：
D'Amore, JD;Kajdasz, ST;Hyman, BT
通讯作者：
Hyman, BT
影响因子：
82.9
作者：
Kukar, T;Murphy, MP;Golde, TE
通讯作者：
Golde, TE
影响因子：
8.3
作者：
Acarin, L;González, B;Castellano, B
通讯作者：
Castellano, B
影响因子：
7.3
作者：
Bayón, Y;Alonso, A;Crespo, MS
通讯作者：
Crespo, MS
DOI：
10.1073/pnas.96.9.5274
发表时间：
1999-04-27
影响因子：
11.1
作者：
Knowles, RB;Wyart, C;Hyman, BT
通讯作者：
Hyman, BT