Role of matrix metalloproteinases and therapeutic benefits of their inhibition in spinal cord injury.
Role of matrix metalloproteinases and therapeutic benefits of their inhibition in spinal cord injury.
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DOI：
10.1007/s13311-011-0038-0
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发表时间：
2011-04
影响因子：
5.7
通讯作者：
Noble-Haeusslein, Linda J.
中科院分区：
文献类型：
--
作者：
Zhang, Haoqian;Chang, Mayland;Hansen, Christopher N.;Basso, D. Michele;Noble-Haeusslein, Linda J.
本文将对基质金属蛋白酶（MMPs）及其抑制剂在脊髓损伤（SCI）中的作用进行综述。MMPs在受损脊髓中具有特定的细胞和时间表达模式。在这里，我们考虑它们在急性损伤的脊髓和伤口愈合过程中的不同功能。急性损伤脊髓中MMPs，特别是明胶酶B （MMP-9）的过度活性导致血脊髓屏障被破坏，白细胞涌入损伤脊髓，以及细胞凋亡。MMP-9和MMP-2调节周围神经损伤后的炎症和神经性疼痛，并可能参与sci诱导的疼痛。早期药物抑制MMPs或明胶酶（MMP-2和MMP-9）可改善长期神经系统恢复，并与减少胶质瘢痕和神经性疼痛相关。在伤口愈合过程中，明胶酶A （MMP-2）在限制抑制性胶质瘢痕的形成中起着关键作用，基因缺乏这种蛋白酶的小鼠表现出受损的恢复。总之，这些发现说明了MMPs在SCIs中复杂的、时间上不同的作用。由于早期明胶酶活性是有害的，因此开发专门针对急性脊髓损伤的明胶酶靶向治疗方法正在引起人们的兴趣。因此，我们将重点介绍选择性明胶酶抑制剂的研究进展。本文的在线版本（doi:10.1007/s13311-011-0038-0）包含补充内容，仅供授权用户使用。
This review will focus on matrix metalloproteinases (MMPs) and their inhibitors in the context of spinal cord injury (SCI). MMPs have a specific cellular and temporal pattern of expression in the injured spinal cord. Here we consider their diverse functions in the acutely injured cord and during wound healing. Excessive activity of MMPs, and in particular gelatinase B (MMP-9), in the acutely injured cord contributes to disruption of the blood-spinal cord barrier, and the influx of leukocytes into the injured cord, as well as apoptosis. MMP-9 and MMP-2 regulate inflammation and neuropathic pain after peripheral nerve injury and may contribute to SCI-induced pain. Early pharmacologic inhibition of MMPs or the gelatinases (MMP-2 and MMP-9) results in an improvement in long-term neurological recovery and is associated with reduced glial scarring and neuropathic pain. During wound healing, gelatinase A (MMP-2) plays a critical role in limiting the formation of an inhibitory glial scar, and mice that are genetically deficient in this protease showed impaired recovery. Together, these findings illustrate complex, temporally distinct roles of MMPs in SCIs. As early gelatinase activity is detrimental, there is an emerging interest in developing gelatinase-targeted therapeutics that would be specifically tailored to the acute injured spinal cord. Thus, we focus this review on the development of selective gelatinase inhibitors. The online version of this article (doi:10.1007/s13311-011-0038-0) contains supplementary material, which is available to authorized users.
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