Inhibiting the DNA damage response pathway promotes functional recovery after spinal cord injury
Inhibiting the DNA damage response pathway promotes functional recovery after spinal cord injury
复制标题
抑制DNA损伤反应途径促进脊髓损伤后功能恢复
DOI：
10.1002/ctd2.106
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Ahmed Z
中科院分区：
文献类型：
--
作者：
Ahmed Z
脊髓损伤 (SCI) 每年影响多达 126 万人，导致永久性残疾和死亡。 SCI 的最大原因是机动车事故、跌倒和人际暴力，临床结果很大程度上取决于病变的严重程度和位置。通常，损伤平面以下会出现运动或感觉功能丧失。目前，SCI 患者没有恢复性治疗，只能提供姑息治疗，而中枢神经系统内在再生能力低下，情况进一步复杂化。 Tuxworth 和 Ahmed 最近发表在《临床与转化医学》上的一项研究表明，抑制共济失调毛细血管扩张突变 (ATM) 激酶（DNA 损伤反应途径的中心调节因子）可促进小鼠和大鼠 SCI 后的轴突再生，并显着改善感觉和运动功能。此外，ATM 抑制剂 AZD1390 具有强效、高选择性、口服生物利用度和脑渗透性。2AZD1390 目前正在开发用于治疗脑癌，但由于其简单的给药途径（口服），有可能重新用于 SCI。
Spinal cord injury (SCI) affects up to 1.26 million people every year, leading to permanent disability and death. The biggest causes of SCI are motor vehicle accidents, falls and interpersonal violence with clinical outcomes very much dependent on the severity and location of the lesion. Frequently, there is loss of motor or sensory function below the level of injury. At present, there are no restorative treatments for SCI patients, with only palliative treatments on offer and complicated further by the low intrinsic capacity of the central nervous system to regenerate. A recent study by Tuxworth and Ahmed, published inClinical and Translational Medicine1shows that inhibiting ataxia‐telangiectasia mutated (ATM) kinase, a central regulator of the DNA damage response pathway, promoted axon regeneration and remarkable improvements in sensory and motor function after SCI in both mice and rats. Moreover, the ATM inhibitor, AZD1390, is potent and highly selective, orally bioavailable and brain‐penetrant.2AZD1390 is currently being developed for the treatment of brain cancers but with its simple route of administration (oral), has the potential to be re‐purposed for use in SCI.
影响因子：
16.6
作者：
Balmus, Gabriel;Pilger, Domenic;Jacksom, Stephen P.
通讯作者：
Jacksom, Stephen P.