Pharmacologically inhibiting kinesin-5 activity with monastrol promotes axonal regeneration following spinal cord injury.
Pharmacologically inhibiting kinesin-5 activity with monastrol promotes axonal regeneration following spinal cord injury.
复制标题
在药理学上抑制抑制运动蛋白5的活性在脊髓损伤后促进轴突再生。
DOI：
10.1016/j.expneurol.2014.10.013
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发表时间：
2015-01
影响因子：
5.3
通讯作者：
Tom, Veronica J.
中科院分区：
文献类型：
--
作者：
Xu, Chen;Klaw, Michelle C.;Lemay, Michel A.;Baas, Peter W.;Tom, Veronica J.
关键词：
虽然成熟神经元的轴突具有较低的再生长能力，但如果为它们的轴突提供允许的基质，例如受损的外周神经，则脊髓损伤（SCI）后某些CNS群体的一些再生是可能的。虽然一些轴突很容易再生成周围神经移植物（PNG），但这些轴突几乎总是在远端界面处停滞，无法重新支配脊髓组织。用软骨素酶ABC（ChABC）治疗远端移植物界面处的胶质瘢痕可以促进再生，但大多数再生的轴突需要进一步刺激以延伸到界面之外。先前的研究表明，抑制性的驱动蛋白-5，一种运动蛋白，以其在有丝分裂中的重要作用而闻名，但也在神经元中表达，与药理学试剂monastrol一起在体外增加轴突在抑制性底物上的生长。我们试图确定SCI后Monastrol治疗是否改善功能性轴突再生。动物接受完整的胸7级（T7）横断和PNG，并鞘内注射ChABC和monastrol或DMSO溶剂。我们发现，ChABC与monastrol相结合显着增强轴突再生。然而，有没有进一步的改善功能或增强c-Fos诱导后，刺激脊髓喙横断。这表明monastrol改善了ChABC介导的轴突再生，但需要进一步的治疗来增强这些再生轴突的整合。
While it is well established that the axons of adult neurons have a lower capacity for regrowth, some regeneration of certain CNS populations after spinal cord injury (SCI) is possible if their axons are provided with a permissive substrate, such as an injured peripheral nerve. While some axons readily regenerate into a peripheral nerve graft (PNG), these axons almost always stall at the distal interface and fail to re-innervate spinal cord tissue. Treatment of the glial scar at the distal graft interface with chondroitinase ABC (ChABC) can improve regeneration, but most regenerated axons need further stimulation to extend beyond the interface. Previous studies demonstrate that pharmacologically inhibiting kinesin-5, a motor protein best known for its essential role in mitosis but also expressed in neurons, with the pharmacological agent monastrol increases axon growth on inhibitory substrates in vitro. We sought to determine if monastrol treatment after a SCI improves functional axon regeneration. Animals received complete thoracic level 7 (T7) transections and PNGs and were treated intrathecally with ChABC and either monastrol or DMSO vehicle. We found that combining ChABC with monastrol significantly enhanced axon regeneration. However, there were no further improvements in function or enhanced c-Fos induction upon stimulation of spinal cord rostral to the transection. This indicates that monastrol improves ChABC-mediated axon regeneration but that further treatments are needed to enhance the integration of these regrown axons.
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影响因子：
3.5
作者：
Sudo, Haruka;Baas, Peter W.
通讯作者：
Baas, Peter W.
DOI：
10.1111/j.1600-0854.2010.01152.x
发表时间：
2011-03
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Lin S;Liu M;Son YJ;Timothy Himes B;Snow DM;Yu W;Baas PW
通讯作者：
Baas PW
DOI：
10.1523/jneurosci.3641-09.2009
发表时间：
2009-11-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Tom VJ;Sandrow-Feinberg HR;Miller K;Santi L;Connors T;Lemay MA;Houlé JD
通讯作者：
Houlé JD
DOI：
10.1016/j.cub.2008.11.021
发表时间：
2008-12-23
期刊：
Current biology : CB
影响因子：
--
作者：
Nadar VC;Ketschek A;Myers KA;Gallo G;Baas PW
通讯作者：
Baas PW
DOI：
10.1007/bf01148324
发表时间：
1984-01-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
RICHARDSON, PM;ISSA, VMK;AGUAYO, AJ
通讯作者：
AGUAYO, AJ