beta-Amyloid-induced neuronal apoptosis requires c-Jun N-terminal kinase activation.
beta-Amyloid-induced neuronal apoptosis requires c-Jun N-terminal kinase activation.
复制标题
β-淀粉样蛋白诱导的神经元凋亡需要 c-Jun N 末端激酶激活。
DOI：
10.1046/j.1471-4159.2001.t01-1-00218.x
复制
发表时间：
2001
影响因子：
4.7
通讯作者：
Greene,LA
中科院分区：
文献类型：
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作者：
Troy,CM;Rabacchi,SA;Xu,Z;Maroney,AC;Connors,TJ;Shelanski,ML;Greene,LA
β‐Amyloid (Aβ) has been strongly implicated in the pathophysiology of Alzheimer's disease (AD), but the means by which the aggregated form of this molecule induces neuronal death have not been fully defined. Here, we examine the role of the c‐Jun N‐terminal kinases (JNKs) and of their substrate, c‐Jun, in the death of cultured neuronal PC12 cells and sympathetic neurons evoked by exposure to aggregated Aβ. The activities of JNK family members increased in neuronal PC12 cells within 2 h of Aβ treatment and reached 3–4‐fold elevation by 6 h. To test the role of these changes in death caused by Aβ, we examined the effects of CEP‐1347 (KT7515), an indolocarbazole that selectively blocks JNK activation. Inclusion of CEP‐1347 (100–300 nm) in the culture medium effectively blocked the increases in cellular JNK activity caused by Aβ and, at similar concentrations, protected both PC12 cells and sympathetic neurons from Aβ‐evoked‐death. Effective protection required addition of CEP‐1347 within 2 h of Aβ treatment, indicating that the JNK pathway acts relatively proximally and as a trigger in the death mechanism. A dominant‐negative c‐Jun construct also conferred protection from Aβ‐evoked death, supporting a model in which JNK activation contributes to death via activation of c‐Jun. Finally, CEP‐1347 blocked Aβ‐stimulated activation of caspase‐2 and ‐3, placing these downstream of JNK activation. These observations implicate the JNK pathway as a required element in death evoked by Aβ and hence identify it as a potential therapeutic target in AD.
DOI：
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发表时间：
1987
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影响因子：
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作者：
B. S. L. CooperGibson;L. Mowafy;D. Tataryn
通讯作者：
D. Tataryn
Watabe，H.；Liang，X.C.：动物学。
DOI：
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发表时间：
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