Trehalose inhibits ferroptosis via NRF2/HO-1 pathway and promotes functional recovery in mice with spinal cord injury.
Trehalose inhibits ferroptosis via NRF2/HO-1 pathway and promotes functional recovery in mice with spinal cord injury.
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DOI：
10.18632/aging.204009
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发表时间：
2022-04-10
期刊：
影响因子：
5.2
通讯作者：
Hu, Baiwen
中科院分区：
文献类型：
--
作者：
Gong, Fangyi;Ge, Ting;Liu, Jing;Xiao, Jin;Wu, Xiaochuan;Wang, Hehui;Zhu, Yingchun;Xia, Dongdong;Hu, Baiwen
脊髓损伤（Spinal cord injury，SCI）是中枢神经系统严重损伤的主要原因，可导致不可逆的组织缺损和神经功能障碍。铁凋亡是近年来新发现的一种细胞死亡模式。铁凋亡是一种由小分子物质诱导的氧化性细胞死亡，是细胞内脂质活性氧（ROS）的产生和降解失衡引起的铁依赖性过程。海藻糖作为一种抗氧化剂，能有效地防止脂质过氧化。研究表明海藻糖可以改善脊髓损伤的预后。然而，目前尚不清楚这些益处是否与铁凋亡有关。本研究首次证明海藻糖通过抑制脊髓损伤后ROS的产生和脂质过氧化物引起的铁凋亡，减少神经元的变性和铁积累，从而促进神经元的存活，改善运动功能的恢复。更具体地说，我们发现海藻糖抑制SCI小鼠神经组织中空洞的扩张，抑制神经元丢失，并改善功能恢复。在机制方面，我们的研究结果表明，海藻糖的神经保护作用是由于激活NRF 2/HO-1通路，从而抑制铁凋亡和铁凋亡相关的炎症。我们的研究结果为以前未知的海藻糖在SCI中的作用提供了重要的见解，以及支持抑制铁凋亡在SCI中起关键神经保护作用的假设的新证据。
Spinal cord injury (SCI) is the main cause of severe damage to the central nervous system and leads to irreversible tissue loss and neurological dysfunction. Ferroptosis is a cell death pattern, newly discovered in recent years. Ferroptosis is an oxidizing cell death induced by small molecules, and is an iron-dependent process caused by the imbalance between the generation and degradation of lipid reactive oxygen species (ROS) in cells. As an antioxidant, trehalose can effectively prevent lipid peroxidation. Studies have reported that trehalose can improve the prognosis of SCI. However, it is unclear whether these benefits are related to ferroptosis. In this study, we demonstrated for the first time that trehalose reduces the degeneration and iron accumulation of neurons by inhibiting the production of ROS and ferroptosis caused by lipid peroxides after SCI, thus promoting the survival of neurons and improving the recovery of motor function. More specifically, we found that trehalose inhibited the expansion of cavities in the nerve tissue of mice with SCI, inhibited neuron loss, and improved functional recovery. In terms of mechanism, our results indicate that the neuroprotective effect of trehalose is due to the activation of the NRF2/HO-1 pathway, which in turn inhibits ferroptosis and ferroptosis-related inflammation. Our findings provide important insights into the previously unknown role of trehalose in SCI, as well as new evidence supporting the hypothesis that suppression of ferroptosis plays a key neuroprotective role in SCI.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
DOI：
10.1073/pnas.1415518111
发表时间：
2014-11-25
影响因子：
11.1
作者：
Linkermann, Andreas;Skouta, Rachid;Krautwald, Stefan
通讯作者：
Krautwald, Stefan
影响因子：
3.3
作者：
Fan B;Wei Z;Yao X;Shi G;Cheng X;Zhou X;Zhou H;Ning G;Kong X;Feng S
通讯作者：
Feng S
影响因子：
3.3
作者：
Du, Jing;Liang, Yu;Wang, Zhao
通讯作者：
Wang, Zhao
DOI：
10.1073/pnas.0905437106
发表时间：
2010-02-23
影响因子：
11.1
作者：
Lee, Hyunjung;McKeon, Robert J.;Bellamkonda, Ravi V.
通讯作者：
Bellamkonda, Ravi V.