NADPH oxidases in traumatic brain injury - Promising therapeutic targets?
NADPH oxidases in traumatic brain injury - Promising therapeutic targets?
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DOI：
10.1016/j.redox.2018.03.005
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发表时间：
2018-06
期刊：
影响因子：
11.4
通讯作者：
Brann DW
中科院分区：
文献类型：
--
作者：
Ma MW;Wang J;Dhandapani KM;Wang R;Brann DW
外伤性脑损伤（TBI）是世界范围内造成死亡和残疾的主要原因。尽管进行了大量的研究，但目前还没有针对创伤性脑损伤的神经保护剂应用于临床。最近的努力集中在确定潜在的治疗靶点，这些靶点是继发性TBI病理的基础，在初始损伤后几分钟到几年内发展。氧化应激在继发性损伤机制的复杂级联中起着关键作用，在神经变性和神经炎症中起着重要作用。NADPH氧化酶（NOX）是一类酶，其独特的功能是产生活性氧（ROS）。人类死后和动物研究发现，损伤脑中NOX2和NOX4水平升高，表明这两种NOXs参与了TBI的发病机制。为了支持这一点，NOX2和NOX4缺失的研究共同表明，靶向NOX酶可以减少氧化应激，减轻神经炎症，促进神经元存活，改善TBI后的功能结局。此外，NOX抑制剂的研究证实了这些发现，并证明了有效治疗TBI的关键窗口延长。最后，该领域的翻译潜力、注意事项和未来方向在整个综述中得到强调和讨论。
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Despite intense investigation, no neuroprotective agents for TBI have yet translated to the clinic. Recent efforts have focused on identifying potential therapeutic targets that underlie the secondary TBI pathology that evolves minutes to years following the initial injury. Oxidative stress is a key player in this complex cascade of secondary injury mechanisms and prominently contributes to neurodegeneration and neuroinflammation. NADPH oxidase (NOX) is a family of enzymes whose unique function is to produce reactive oxygen species (ROS). Human post-mortem and animal studies have identified elevated NOX2 and NOX4 levels in the injured brain, suggesting that these two NOXs are involved in the pathogenesis of TBI. In support of this, NOX2 and NOX4 deletion studies have collectively revealed that targeting NOX enzymes can reduce oxidative stress, attenuate neuroinflammation, promote neuronal survival, and improve functional outcomes following TBI. In addition, NOX inhibitor studies have confirmed these findings and demonstrated an extended critical window of efficacious TBI treatment. Finally, the translational potential, caveats, and future directions of the field are highlighted and discussed throughout the review.
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