SOD2
活性氧
抗氧化剂
神经保护
化学
细胞生物学
氧化应激
内生
药理学
胞浆
冲程(发动机)
生物化学
超氧化物歧化酶
酶
医学
生物
工程类
机械工程
作者
Jian Wang,Yang Wang,Xiakeerzhati Xiaohalati,Qiangfei Su,Jingwei Liu,Bo Cai,Wen Yang,Zheng Wang,Lin Wang
标识
DOI:10.1002/advs.202206854
摘要
Abstract Following stroke, oxidative stress induced by reactive oxygen species (ROS) aggravates neuronal damage and enlarges ischemic penumbra, which is devastating to stroke patients. Nanozyme-based antioxidants are emerging to treat stroke through scavenging excessive ROS. However, most of nanozymes cannot efficiently scavenge ROS in neuronal cytosol and mitochondria, due to low-uptake abilities of neurons and barriers of organelle membranes, significantly limiting nanozymes’ neuroprotective effects. To overcome this limitation, a manganese-organic framework modified with polydopamine (pDA-MNOF), capable of not only mimicking catalytic activities of natural SOD2's catalytic domain but also upregulating two endogenous antioxidant enzymes in neurons is fabricated. With such a dual anti-ROS effect, this nanozyme robustly decreases cellular ROS and effectively protects them from ROS-induced injury. STAT-3 signaling is found to play a vital role in pDA-MNOF activating the two antioxidant enzymes, HO1 and SOD2. In vivo pDA-MNOF treatment significantly improves the survival of middle cerebral artery occlusion (MCAo) mice by reducing infarct volume and more importantly, promotes animal behavioral recovery. Further, pDA-MNOF activates vascular endothelial growth factor expression, a downstream target of STAT3 signaling, thus enhancing angiogenesis. Taken together, the biochemical, cell-biological, and animal-level behavioral data demonstrate the potentiality of pDA-MNOF as a dual ROS-scavenging agent for stroke treatment.
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