Axonal regeneration. Systemic administration of epothilone B promotes axon regeneration after spinal cord injury.
Axonal regeneration. Systemic administration of epothilone B promotes axon regeneration after spinal cord injury.
复制标题
DOI：
10.1126/science.aaa2958
复制
发表时间：
2015-04-17
期刊：
影响因子：
--
通讯作者：
Bradke F
中科院分区：
文献类型：
--
作者：
Ruschel J;Hellal F;Flynn KC;Dupraz S;Elliott DA;Tedeschi A;Bates M;Sliwinski C;Brook G;Dobrindt K;Peitz M;Brüstle O;Norenberg MD;Blesch A;Weidner N;Bunge MB;Bixby JL;Bradke F
中枢神经系统(CNS)损伤后，损伤瘢痕中的抑制因子和不良的轴突生长潜能阻碍了轴突再生。微管稳定减少疤痕，促进轴突生长。然而，这种双重效应的细胞机制仍不清楚。在这里，延迟全身给药血脑屏障通透性微管稳定剂Epothilone B，通过消除极化和瘢痕形成的成纤维细胞的定向迁移来减少啮齿动物脊髓损伤(SCI)后的瘢痕形成。相反，Epothilone B通过诱导协调的微管聚合进入轴突尖端，重新激活神经元极化，从而推动轴突生长穿过抑制环境。总之，这些药物具有促进脊髓损伤后轴突再生和改善运动功能的作用。随着最近的临床批准，埃博西酮有望在中枢神经系统损伤后应用于临床。
After central nervous system (CNS) injury, inhibitory factors in the lesion scar and a poor axon growth potential prevent axon regeneration. Microtubule stabilization reduces scarring and promotes axon growth. However, the cellular mechanisms of this dual effect remain unclear. Here, delayed systemic administration of a blood-brain barrier permeable microtubule stabilizing drug, epothilone B, decreased scarring after rodent spinal cord injury (SCI) by abrogating polarization and directed migration of scar-forming fibroblasts. Conversely, epothilone B reactivated neuronal polarization by inducing concerted microtubule polymerization into the axon tip, which propelled axon growth through an inhibitory environment. Together, these drug elicited effects promoted axon regeneration and improved motor function after SCI. With recent clinical approval, epothilones hold promise for clinical use after CNS injury.
登录
查看更多内容
影响因子：
5.3
作者：
WRATHALL, JR;PETTEGREW, RK;HARVEY, F
通讯作者：
HARVEY, F
影响因子：
64.5
作者：
Lu P;Wang Y;Graham L;McHale K;Gao M;Wu D;Brock J;Blesch A;Rosenzweig ES;Havton LA;Zheng B;Conner JM;Marsala M;Tuszynski MH
通讯作者：
Tuszynski MH
DOI：
10.1073/pnas.0408974102
发表时间：
2005-06-07
影响因子：
11.1
作者：
Rouzier, R;Rajan, R;Pusztai, L
通讯作者：
Pusztai, L
影响因子：
16.2
作者：
Kim, JE;Liu, BP;Strittmatter, SM
通讯作者：
Strittmatter, SM
影响因子：
15.9
作者：
Fellner, S;Bauer, B;Fricker, G
通讯作者：
Fricker, G