A small molecule for stroke therapy Better therapies for motor impairments after stroke are greatly needed. In mice and nonhuman primates, Abe et al. found that edonerpic maleate enhanced synaptic plasticity and functional recovery after a traumatic insult to the brain (see the Perspective by Rumpel). This recovery of motor function was accompanied by functional reorganization of the cortex. Science, this issue p. 50; see also p. 30 A small neuroprotective molecule improves motor function after brain injury in mice and macaques. 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 (α-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.

中文翻译：

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CRMP2 结合化合物，依多皮马来酸盐，加速脑损伤后运动功能的恢复

用于中风治疗的小分子非常需要针对中风后运动障碍的更好疗法。在小鼠和非人类灵长类动物中，Abe 等人。发现 edonerpic maleate 增强了大脑遭受创伤后的突触可塑性和功能恢复（参见 Rumpel 的观点）。这种运动功能的恢复伴随着皮层的功能重组。科学，这个问题 p。50; 另见第。30 一种小的神经保护分子可改善小鼠和猕猴脑损伤后的运动功能。中风等脑损伤是一种破坏性的神经系统疾病，可能会严重影响患者的生活质量。尚未建立有效的药物介导干预来加速康复。我们发现了一种小的化合物，依多皮马来酸盐，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，并导致训练依赖性小鼠运动皮层冷冻损伤后运动功能恢复的加速通过皮层重组的方式。Edonerpic 与折叠蛋白反应介体蛋白 2 (CRMP2) 结合，但未能增加 CRMP2 缺陷小鼠的恢复。Edonerpic马来酸盐增强了非人类灵长类动物内囊出血的运动功能恢复。因此，edonerpic maleate，一种神经可塑性增强剂，可能是一种临床上有效的小化合物，用于加速脑损伤后的康复。