CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage

被引:67
作者
Abe, Hiroki [1 ]
Jitsuki, Susumu [1 ]
Nakajima, Waki [1 ]
Murata, Yumi [2 ]
Jitsuki-Takahashi, Aoi [1 ]
Katsuno, Yuki [1 ]
Tada, Hirobumi [1 ]
Sano, Akane [1 ]
Suyama, Kumiko [1 ]
Mochizuki, Nobuyuki [1 ,3 ,4 ]
Komori, Takashi [1 ,3 ,4 ]
Masuyama, Hitoshi [1 ,3 ,4 ]
Okuda, Tomohiro [3 ,4 ]
Goshima, Yoshio [5 ]
Higo, Noriyuki [2 ]
Takahashi, Takuya [1 ]
机构
[1] Yokohama City Univ, Grad Sch Med, Dept Physiol, Yokohama, Kanagawa 2360004, Japan
[2] Natl Inst Adv Ind Sci & Technol, Human Informat Res Inst, Tsukuba 3058568, Japan
[3] Toyama Chem Co, Tokyo 1600023, Japan
[4] Fujifilm Corp, Tokyo 1070052, Japan
[5] Yokohama City Univ, Grad Sch Med, Dept Mol Pharmacol & Neurobiol, Yokohama, Kanagawa 2360004, Japan
关键词
AMPA RECEPTOR DELIVERY; SPINAL-CORD-INJURY; SYNAPTIC PLASTICITY; SQUIRREL-MONKEYS; ISCHEMIC INFARCT; ACTIN DYNAMICS; TRAFFICKING; STROKE; CORTEX; REORGANIZATION;
D O I
10.1126/science.aao2300
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:50 / 57
页数:8
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