Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: From tuberous sclerosis to common acquired epilepsies.
Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: From tuberous sclerosis to common acquired epilepsies.
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DOI：
10.1111/j.1528-1167.2009.02341.x
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发表时间：
2010-01
期刊：
影响因子：
5.6
通讯作者：
Wong M
中科院分区：
文献类型：
--
作者：
Wong M
目前大多数癫痫治疗都是对症治疗，抑制癫痫发作，但不影响癫痫的基本病程或预后。人们广泛认识到对癫痫病进行疾病缓解或“抗癫痫原”治疗的需要，但尚未建立用于临床的此类预防性疗法。预防癫痫的合理策略是针对最初触发介导癫痫发生的众多下游机制的主要信号传导途径。哺乳动物雷帕霉素靶点 (mTOR) 通路代表了一个合理的候选者，因为 mTOR 调节可能有助于癫痫发生的多种细胞功能，包括蛋白质合成、细胞生长和增殖以及突触可塑性。结节性硬化症 (TSC) 是癫痫最常见的遗传原因之一，这最好地说明了 mTOR 通路在癫痫发生中的重要性。在 TSC 小鼠模型中，mTOR 抑制剂可预防癫痫的发展以及与癫痫发生相关的潜在大脑异常。越来越多的证据表明，mTOR 还参与多种其他原因导致的癫痫发生，包括局灶性皮质发育不良和获得性脑损伤，例如在癫痫持续状态或创伤性脑损伤后的动物模型中。因此，mTOR 抑制可能代表一种针对多种类型癫痫（包括遗传性癫痫和获得性癫痫）的潜在抗癫痫发生疗法。
Most current treatments for epilepsy are symptomatic therapies that suppress seizures but do not affect the underlying course or prognosis of epilepsy. The need for disease-modifying or “antiepileptogenic” treatments for epilepsy is widely recognized, but no such preventative therapies have yet been established for clinical use. A rational strategy for preventing epilepsy is to target primary signaling pathways that initially trigger the numerous downstream mechanisms mediating epileptogenesis. The mammalian target of rapamycin (mTOR) pathway represents a logical candidate, because mTOR regulates multiple cellular functions that may contribute to epileptogenesis, including protein synthesis, cell growth and proliferation, and synaptic plasticity. The importance of the mTOR pathway in epileptogenesis is best illustrated by Tuberous Sclerosis Complex (TSC), one of the most common genetic causes of epilepsy. In mouse models of TSC, mTOR inhibitors prevent the development of epilepsy and underlying brain abnormalities associated with epileptogenesis. Accumulating evidence suggests that mTOR also participates in epileptogenesis due to a variety of other causes, including focal cortical dysplasia and acquired brain injuries, such as in animal models following status epilepticus or traumatic brain injury. Thus, mTOR inhibition may represent a potential antiepileptogenic therapy for diverse types of epilepsy, including both genetic and acquired epilepsies.
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影响因子：
3.6
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影响因子：
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