CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage
CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage
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DOI：
10.1126/science.aao2300
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发表时间：
2018-04-06
期刊：
影响因子：
56.9
通讯作者：
Takahashi, Takuya
中科院分区：
文献类型：
--
作者：
Abe, Hiroki;Jitsuki, Susumu;Takahashi, Takuya
脑损伤（如中风）是一种毁灭性的神经系统疾病，可能严重影响患者的生活质量。没有建立有效的药物介导的干预措施，以加速康复。我们发现，一种小分子化合物，马来酸依多奈平，促进经验驱动的突触谷氨酸AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸）受体的传递，并导致在运动皮层冷冻损伤后，通过皮层重组以训练依赖的方式在小鼠运动功能恢复的加速。Edonerpic结合到胰蛋白酶反应介导蛋白2（CRMP 2），并未能增加CRMP 2缺陷小鼠的恢复。马来酸依度能促进非人灵长类动物内囊出血后运动功能的恢复。因此，马来酸依多奈匹克，一种神经可塑性增强剂，可能是一种临床上有效的小分子化合物，可以加速脑损伤后的康复。
Brain damage such as stroke is a devastating neurological condition that may severely compromise patient quality of life. No effective medication-mediated intervention to accelerate rehabilitation has been established. We found that a small compound, edonerpic maleate, facilitated experience-driven synaptic glutamate AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic-acid) receptor delivery and resulted in the acceleration of motor function recovery after motor cortex cryoinjury in mice in a training-dependent manner through cortical reorganization. Edonerpic bound to collapsin-response-mediator-protein 2 (CRMP2) and failed to augment recovery in CRMP2-deficient mice. Edonerpic maleate enhanced motor function recovery from internal capsule hemorrhage in nonhuman primates. Thus, edonerpic maleate, a neural plasticity enhancer, could be a clinically potent small compound with which to accelerate rehabilitation after brain damage.