Inhibition of c-Jun kinase provides neuroprotection in a model of Alzheimer's disease.
Inhibition of c-Jun kinase provides neuroprotection in a model of Alzheimer's disease.
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DOI：
10.1016/j.nbd.2010.04.015
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发表时间：
2010-09
影响因子：
6.1
通讯作者：
Lo DC
中科院分区：
文献类型：
--
作者：
Braithwaite SP;Schmid RS;He DN;Sung ML;Cho S;Resnick L;Monaghan MM;Hirst WD;Essrich C;Reinhart PH;Lo DC
c-Jun n -末端激酶（JNK）通路可能将阿尔茨海默病（AD）的三个主要病理标志联系在一起：淀粉样斑块的发展、神经原纤维缠结和脑萎缩。正如我们在Tg2576/PSM146L转基因小鼠中证实的那样，在AD的淀粉样蛋白模型中已经观察到JNK通路的激活与斑块周围区域和神经性营养不良有关，我们直接测试了JNK抑制是否可以在淀粉样蛋白前体蛋白（APP）诱导的神经变性的新型脑切片模型中提供神经保护。我们发现APP/ β淀粉样蛋白（Aβ）诱导的神经变性被JNK的小分子和肽抑制剂阻断，并提供证据表明这种神经保护发生在APP/Aβ生产和加工的下游。我们的研究结果表明，Aβ可以诱导神经退行性变，至少部分通过JNK途径，并提示抑制JNK可能在治疗AD中具有治疗效用。
The c-Jun N-terminal kinase (JNK) pathway potentially links together the three major pathological hallmarks of Alzheimer’s disease (AD): development of amyloid plaques, neurofibrillary tangles, and brain atrophy. As activation of the JNK pathway has been observed in amyloid models of AD in association with peri-plaque regions and neuritic dystrophy, as we confirm here for Tg2576/PSM146L transgenic mice, we directly tested whether JNK inhibition could provide neuroprotection in a novel brain slice model for amyloid precursor protein (APP)-induced neurodegeneration. We found that APP/amyloid β (Aβ)-induced neurodegeneration is blocked by both small molecule and peptide inhibitors of JNK, and provide evidence that this neuroprotection occurs downstream of APP/Aβ production and processing. Our findings demonstrate that Aβ can induce neurodegeneration, at least in part, through the JNK pathway and suggest that inhibition of JNK may be of therapeutic utility in the treatment of AD.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
影响因子：
82.9
作者：
Holcomb, L;Gordon, MN;Duff, K
通讯作者：
Duff, K
影响因子：
3.5
作者：
Pu, Jun;Kreft, Anthony F.;Resnick, Lynn
通讯作者：
Resnick, Lynn
影响因子：
4.2
作者：
Quiroz-Baez, Ricardo;Rojas, Emilio;Arias, Clorinda
通讯作者：
Arias, Clorinda
影响因子：
8.3
作者：
Fisher M;Feuerstein G;Howells DW;Hurn PD;Kent TA;Savitz SI;Lo EH;STAIR Group
通讯作者：
STAIR Group