Plasmalogens Activate AKT/mTOR Signaling to Attenuate Reactive Oxygen Species Production in Spinal Cord Injury.

IF 3.8 4区医学 Q2 GENETICS & HEREDITY

Current gene therapy Pub Date : 2025-01-20 DOI:10.2174/0115665232330349241225074627

Mengdan Cheng, Yan Gao, Yiqing Wu, Liangliang Zhang, Bai Xu, Xiaojie Lu

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引用次数: 0

Abstract

Background: Plasmalogens, the primary phospholipids in the brain, possess intrinsic antioxidant properties and are crucial components of the myelin sheath surrounding neuronal axons. While their neuroprotective effects have been demonstrated in Alzheimer's disease, their potential benefits in spinal cord injury remain unexplored. This study investigates the reparative effects of plasmalogens on spinal cord injury and the underlying mechanisms.

Methods: In vitro, we developed dorsal root ganglion (DRG) and RAW 264.7 cell models under high-reactive oxygen species (ROS) conditions to assess ROS levels, neuronal damage, and inflammatory microenvironment changes before and after plasmalogen application. In vivo, we used a complete mouse spinal cord transection model to evaluate changes in ROS levels, neuronal demyelination, and apoptosis following plasmalogen treatment. Additionally, we assessed sensory and motor function recovery and investigated the regulatory effects of plasmalogens on the AKT/mTOR signaling pathway.

Results: In high-ROS cell models, plasmalogens protected DRG neurons (TUJ-1) from axonal damage and modulated the proinflammatory/anti-inflammatory balance in RAW 264.7 cells. In vivo, plasmalogens significantly reduced ROS levels, improved the immune microenvironment, decreased the proinflammatory (iNOS)/anti-inflammatory (ARG-1) ratio, lowered neuronal (TUJ-1) apoptosis (Caspase-3, BAX), and reduced axonal degeneration while promoting myelin (MBP) regeneration, indicating a neuroprotective effect. These findings are linked to the activation of the AKT/mTOR signaling pathway.

Conclusion: Plasmalogens reduce ROS levels and regulate inflammation-induced damage, contributing to neuroprotection. This study reveals that plasmalogens promote remyelination, reduce axonal degeneration and neuronal apoptosis, and-used here for the first time in spinal cord injury repair- may protect neurons by reducing ROS levels and activating the AKT/mTOR signaling pathway.

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缩醛磷脂激活AKT/mTOR信号减少脊髓损伤中活性氧的产生

背景：缩醛磷脂是大脑中的主要磷脂，具有内在的抗氧化特性，是神经轴突周围髓鞘的重要组成部分。虽然它们对阿尔茨海默病的神经保护作用已被证实，但它们对脊髓损伤的潜在益处仍未被探索。本研究探讨磷脂原对脊髓损伤的修复作用及其机制。方法：在体外建立高活性氧（ROS）条件下的背根神经节（DRG）和RAW 264.7细胞模型，评估应用plasmalogen前后ROS水平、神经元损伤和炎症微环境的变化。在体内，我们使用完整的小鼠脊髓横断模型来评估等离子原治疗后ROS水平、神经元脱髓鞘和细胞凋亡的变化。此外，我们评估了感觉和运动功能恢复，并研究了磷脂原对AKT/mTOR信号通路的调节作用。结果：在高ros细胞模型中，浆磷脂原可保护DRG神经元（TUJ-1）免受轴突损伤，并调节RAW 264.7细胞的促炎/抗炎平衡。在体内，缩醛磷脂显著降低ROS水平，改善免疫微环境，降低促炎(iNOS)/抗炎（ARG-1）比，降低神经元（TUJ-1）凋亡（Caspase-3， BAX），减少轴突变性，促进髓鞘（MBP）再生，表明其具有神经保护作用。这些发现与AKT/mTOR信号通路的激活有关。结论：缩醛磷脂原可降低ROS水平，调节炎症损伤，具有一定的神经保护作用。本研究揭示，磷脂原可能通过降低ROS水平和激活AKT/mTOR信号通路来保护神经元，促进髓鞘再生，减少轴突变性和神经元凋亡，并首次用于脊髓损伤修复。

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来源期刊

Current gene therapy 医学-遗传学

CiteScore

6.70

自引率

2.80%

发文量

期刊介绍： Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.