Aiming for the target: Mitochondrial drug delivery in traumatic brain injury.
Aiming for the target: Mitochondrial drug delivery in traumatic brain injury.
复制标题
瞄准目标：创伤性脑损伤中的线粒体药物递送。
DOI：
10.1016/j.neuropharm.2018.07.014
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发表时间：
2019-03
影响因子：
4.7
通讯作者：
Bayır H
中科院分区：
文献类型：
--
作者：
Lamade AM;Kenny EM;Anthonymuthu TS;Soysal E;Clark RSB;Kagan VE;Bayır H
线粒体是神经元功能的基石，具有生命的维持者和死亡的先兆的双重作用。虽然线粒体对于能量生产是不可或缺的，但一个失调的线粒体网络可能会给神经元及其提供的功能带来厄运。创伤性脑损伤是一种复杂的双相性损伤，常累及儿童和青壮年。颅脑损伤的主要病理机制是机械性的，太快了，只有预防才能减轻。然而，颅脑损伤的继发性损伤在最初的伤害后几个小时和几天内发展，为干预提供了机会之窗。作为第二阶段生存和死亡的连接点，靶向脑损伤的线粒体病理长期以来一直是一个有吸引力的策略。这些尝试往往受制于药效限制的意外脱靶效应。治疗药物在其线粒体下作用部位的特定递送和浓缩可以减少有害影响并提高效力。线粒体药物定位是使用(1)线粒体膜电位，(2)载体对线粒体特定成分(如脂质)的亲和力，(3)依靠细胞自身的线粒体运输系统，或(4)基于纳米颗粒的方法来完成的。在这篇综述中，我们简要地讨论了线粒体递送策略和药物靶点，说明了这些线粒体特异性方法在脑外伤药物治疗设计中的前景。
Mitochondria are a keystone of neuronal function, serving a dual role as sustainer of life and harbinger of death. While mitochondria are indispensable for energy production, a dysregulated mitochondrial network can spell doom for both neurons and the functions they provide. Traumatic brain injury (TBI) is a complex and biphasic injury, often affecting children and young adults. The primary pathological mechanism of TBI is mechanical, too rapid to be mitigated by anything but prevention. However, the secondary injury of TBI evolves over hours and days after the initial insult providing a window of opportunity for intervention. As a nexus point of both survival and death during this second phase, targeting mitochondrial pathology in TBI has long been an attractive strategy. Often these attempts are mired by efficacy-limiting unintended off-target effects. Specific delivery to and enrichment of therapeutics at their submitochondrial site of action can reduce deleterious effects and increase potency. Mitochondrial drug localization is accomplished using (1) the mitochondrial membrane potential, (2) affinity of a carrier to mitochondria-specific components (e.g. lipids), (3) piggybacking on the cells own mitochondria trafficking systems, or (4) nanoparticle-based approaches. In this review, we briefly consider the mitochondrial delivery strategies and drug targets that illustrate the promise of these mitochondria-specific approaches in the design of TBI pharmacotherapy.
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影响因子：
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