Carbamazepine Restores Neuronal Signaling, Protein Synthesis, and Cognitive Function in a Mouse Model of Fragile X Syndrome.
Carbamazepine Restores Neuronal Signaling, Protein Synthesis, and Cognitive Function in a Mouse Model of Fragile X Syndrome.
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DOI：
10.3390/ijms21239327
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发表时间：
2020-12-07
影响因子：
5.6
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Ding Q;Zhang F;Feng Y;Wang H
脆性X综合征(FXS)是由功能性脆性X智力低下蛋白(FMRP)缺失引起的一种主要的遗传性智能障碍。到目前为止，还没有有效的基于机制的药物治疗FXS。关于FXS的潜在发病机制，人们普遍认为FMRP的缺乏会导致蛋白质合成增加和神经元信号转导的紊乱。在FXS患者和FXS小鼠模型中，都发现ERKç(细胞外信号调节激酶1/2)和PI3K-Akt(磷脂酰肌醇3激酶-蛋白激酶B)信号通路异常增强。在这项研究中，我们证明了卡马西平是FDA批准的药物，主要用于治疗癫痫和神经病理性疼痛，纠正了FXS小鼠的认知缺陷，包括被动回避和物体位置记忆。卡马西平还可以挽救过度运动和社会缺陷。在细胞水平上，卡马西平抑制FXS小鼠神经元ERK和Akt信号水平的升高以及蛋白质的合成。总之，这些结果支持将卡马西平重新用于FXS治疗。
Fragile X syndrome (FXS) is a leading genetic disorder of intellectual disability caused by the loss of the functional fragile X mental retardation protein (FMRP). To date, there is no efficacious mechanism-based medication for FXS. With regard to potential disease mechanisms in FXS, it is widely accepted that the lack of FMRP causes elevated protein synthesis and deregulation of neuronal signaling. Abnormal enhancement of the ERK½ (extracellular signal-regulated kinase ½) and PI3K-Akt (Phosphoinositide 3 kinase-protein kinase B) signaling pathways has been identified in both FXS patients and FXS mouse models. In this study, we show that carbamazepine, which is an FDA-approved drug and has been mainly used to treat seizure and neuropathic pain, corrects cognitive deficits including passive avoidance and object location memory in FXS mice. Carbamazepine also rescues hyper locomotion and social deficits. At the cellular level, carbamazepine dampens the elevated level of ERK½ and Akt signaling as well as protein synthesis in FXS mouse neurons. Together, these results advocate repurposing carbamazepine for FXS treatment.
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影响因子：
3.7
作者：
Maurin, Thomas;Melancia, Francesca;Bardoni, Barbara
通讯作者：
Bardoni, Barbara
影响因子：
4.6
作者：
Gurney ME;Cogram P;Deacon RM;Rex C;Tranfaglia M
通讯作者：
Tranfaglia M
DOI：
10.1007/978-1-62703-520-0_21
发表时间：
2013
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Chen SH;Oyarzabal EA;Hong JS
通讯作者：
Hong JS
DOI：
10.1002/ajmg.1320450120
发表时间：
1993-01-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
BERRYKRAVIS, E;SKLENA, P
通讯作者：
SKLENA, P
影响因子：
2.7
作者：
Assini, Fabricio Luiz;Duzzioni, Marcelo;Takahashi, Reinaldo Naoto
通讯作者：
Takahashi, Reinaldo Naoto