首页> 外文期刊>The Open Drug Discovery Journal >Proteolytic Extracellular Matrix Fragments Following Ischemic Stroke: New Insights to Potential Therapeutic Targets
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Proteolytic Extracellular Matrix Fragments Following Ischemic Stroke: New Insights to Potential Therapeutic Targets

机译:缺血性中风后蛋白水解的细胞外基质片段:对潜在治疗目标的新见解。

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Stroke is the leading cause of long-term disability and the third leading cause of death in the United States. Thesudden disruption of blood flow that occurs following ischemic stroke ultimately leads to neuronal death, breakdown ofthe blood brain barrier, and proteolytic processing of the surrounding extracellular matrix (ECM). Within 3 days afterischemic stroke, new blood vessels begin to form around (ischemic penumbra) the site of injury by a process known asangiogenesis. Angiogenesis, in turn is regulated by a number of growth factors and by processed biologically activefragments of the ECM. Unfortunately, current experimental stroke therapies that might enhance post-stroke angiogenesis,including growth factors, pharmaceuticals, and stem cells may engender significant and unacceptable risks. Furthermore,while most other stroke therapies have focused on neuroprotection during the acute phase of stroke injury, we hypothesizethat exploiting brain self-repair mechanisms, including ECM matrix fragment generation, may provide better therapies. Inthis mini-review we will discuss the importance of the ECM following stroke, including the potential role of itsproteolytic fragments in modulating angiogenesis and neurogenesis.
机译:在美国,中风是长期残疾的主要原因,也是第三大死亡原因。缺血性中风后发生的突然血流中断最终导致神经元死亡,血脑屏障破坏以及周围细胞外基质(ECM)的蛋白水解过程。在缺血性中风后的三天内,新血管开始通过血管新生过程在(缺血半影)损伤部位周围形成。血管生成又受许多生长因子和加工过的ECM的生物活性片段的调节。不幸的是,当前的实验性中风疗法可能会增强中风后血管生成,包括生长因子,药物和干细胞,可能会带来重大而无法接受的风险。此外,虽然大多数其他中风疗法都集中在中风损伤急性期的神经保护作用,但我们假设利用脑自我修复机制(包括ECM基质片段生成)可能会提供更好的疗法。在这篇小型综述中,我们将讨论中风后ECM的重要性,包括其蛋白水解片段在调节血管生成和神经发生中的潜在作用。

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