Sirolimus relieves seizures and neuropsychiatric symptoms via changes of microglial polarity in tuberous sclerosis complex model mice
Sirolimus relieves seizures and neuropsychiatric symptoms via changes of microglial polarity in tuberous sclerosis complex model mice
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DOI：
10.1016/j.neuropharm.2022.109203
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发表时间：
2022-08
影响因子：
4.7
通讯作者：
Makiko Koike-Kumagai;M. Fujimoto;M. Wataya-Kaneda
中科院分区：
文献类型：
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作者：
Makiko Koike-Kumagai;M. Fujimoto;M. Wataya-Kaneda
多发性硬化症是一种以系统性错构瘤为特征的神经皮肤综合征，包括皮肤和神经症状。许多患者表现出癫痫、智力残疾、自闭症和其他行为和神经精神症状，称为TSC相关神经精神障碍（TAND）。TSC涉及雷帕霉素（mTOR）的机制靶点，特别是mTOR复合物1（mTORC 1）的过度活化。因此，mTORC 1抑制剂可有效治疗TSC中的脑、肾、肺和皮肤错构瘤。然而，mTORC1抑制剂对TSC患者神经系统症状的影响仍不清楚，尽管有报道称mTORC1抑制剂在动物模型中改善癫痫、行为障碍和学习障碍。
Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome characterized by systemic hamartomas, including skin and neural symptoms. Many patients exhibit epilepsy, intellectual disability, autism, and other behavioral and neuropsychiatric symptoms, referred to as TSCassociated neuropsychiatric disorders (TAND). TSC involves the overactivation of the mechanistic target of rapamycin (mTOR), specifically mTOR complex 1 (mTORC1). Therefore, mTORC1 inhibitors effectively treat brain, kidney, lung, and skin hamartomas in TSC. However, the effect of mTORC1 inhibitors on neurological symptoms in patients with TSC remains unclear, despite reports of mTORC1 inhibitors improving epilepsy, behavioral disorders, and learning disabilities in animal models.