Regulation of cell death and epileptogenesis by the mammalian target of rapamycin (mTOR): a double-edged sword?
Regulation of cell death and epileptogenesis by the mammalian target of rapamycin (mTOR): a double-edged sword?
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DOI：
10.4161/cc.9.12.11866
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发表时间：
2010-06-15
期刊：
影响因子：
--
通讯作者：
Wong M
中科院分区：
文献类型：
--
作者：
Zeng LH;McDaniel S;Rensing NR;Wong M
鉴定介导癫痫相关神经元死亡和癫痫发生的细胞信号传导机制对于开发更有效的癫痫治疗方法是重要的。哺乳动物雷帕霉素靶蛋白（mTOR）通路最近被证实参与调节啮齿动物癫痫模型中的神经元死亡和癫痫发生。特别地，红藻氨酸盐诱导的癫痫持续状态引起mTOR通路的异常激活，并且mTOR抑制剂雷帕霉素可以减少红藻氨酸盐模型中神经元死亡和慢性癫痫发作的发展。在这里，我们讨论了这些发现的意义，并通过确定上游信号通路，通过红藻氨酸癫痫持续状态激活mTOR通路，并通过证明有限的情况下，雷帕霉素可能矛盾地增加mTOR激活和恶化红藻氨酸模型中的神经元死亡，进一步扩展它们。因此，通过mTOR对癫痫诱导的神经元死亡和癫痫发生的调节是复杂的，并且取决于生理和病理背景可能具有双重、相反的作用。总的来说，这些发现对设计调节mTOR通路的潜在神经保护和抗癫痫治疗具有重要意义。
Identification of cell signaling mechanisms mediating seizure-related neuronal death and epileptogenesis is important for developing more effective therapies for epilepsy. The mammalian target of rapamycin (mTOR) pathway has recently been implicated in regulating neuronal death and epileptogenesis in rodent models of epilepsy. In particular, kainate-induced status epilepticus causes abnormal activation of the mTOR pathway, and the mTOR inhibitor, rapamycin, can decrease the development of neuronal death and chronic seizures in the kainate model. Here, we discuss the significance of these findings and extend them further by identifying upstream signaling pathways through which kainate status epilepticus activates the mTOR pathway and by demonstrating limited situations where rapamycin may paradoxically increase mTOR activation and worsen neuronal death in the kainate model. Thus, the regulation of seizure-induced neuronal death and epileptogenesis by mTOR is complex and may have dual, opposing effects depending on the physiological and pathological context. Overall, these findings have important implications for designing potential neuroprotective and antiepileptogenic therapies that modulate the mTOR pathway.
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影响因子：
6.1
作者：
Erlich, S.;Alexandrovich, A.;Pinkas-Kramarski, R.
通讯作者：
Pinkas-Kramarski, R.
影响因子：
4.3
作者：
Ljungberg, M. Cecilia;Sunnen, C. Nicole;D'Arcangelo, Gabriella
通讯作者：
D'Arcangelo, Gabriella
DOI：
10.1073/pnas.95.26.15653
发表时间：
1998-12-22
影响因子：
11.1
作者：
Soucek, T;Yeung, RS;Hengstschläger, M
通讯作者：
Hengstschläger, M
影响因子：
2.1
作者：
Kimura, N;Tokunaga, C;Yonezawa, K
通讯作者：
Yonezawa, K
影响因子：
2.2
作者：
Loescher, Wolfgang;Schmidt, Dieter
通讯作者：
Schmidt, Dieter