Zhao Zhi-Jie, Zheng Rui-Zhe, Wang Xiao-Jing, Li Tong-Qi, Dong Xiao-Hua, Zhao Chang-Yi, Li Xin-Yuan
Department of Neurosurgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Front Aging Neurosci. 2022 Apr 25;14:870957. doi: 10.3389/fnagi.2022.870957. eCollection 2022.
Multiple sclerosis (MS) is an incurable and progressive neurodegenerative disease that affects more than 2.5 million people worldwide and brings tremendous economic pressures to society. However, the pathophysiology of MS is still not fully elucidated, and there is no effective treatment. Demyelination is thought to be the primary pathophysiological alteration in MS, and our previous study found abnormal lipid metabolism in the demyelinated corpus callosum. Growing evidence indicates that central nervous system (CNS) demyelinating diseases never result from one independent factor, and the simultaneous participation of abnormal lipid metabolism, oxidative stress, and neuroinflammation could potentiate each other in the pathogenesis of MS. Therefore, a single omics analysis cannot provide a full description of any neurodegenerative disease. It has been demonstrated that oxidative stress and neuroinflammation are two reciprocal causative reasons for the progression of MS disease. However, the potential crosstalk between oxidative stress and neuroinflammation remains elusive so far. With an integrated analysis of targeted lipidomics and transcriptomics, our research presents the potential interaction between abnormalities of lipid metabolism, mitochondrial dysfunction, oxidative stress, and neuroinflammation in CNS demyelinating diseases. The findings of this paper may be used to identify possible targets for the therapy of CNS demyelinating diseases.
多发性硬化症（MS）是一种无法治愈的进行性神经退行性疾病，全球有超过250万人受其影响，给社会带来了巨大的经济压力。然而，MS的病理生理学仍未完全阐明，且尚无有效的治疗方法。脱髓鞘被认为是MS主要的病理生理改变，我们之前的研究发现脱髓鞘的胼胝体中存在脂质代谢异常。越来越多的证据表明，中枢神经系统（CNS）脱髓鞘疾病并非由单一独立因素导致，脂质代谢异常、氧化应激和神经炎症的共同参与可能在MS的发病机制中相互促进。因此，单一的组学分析无法全面描述任何神经退行性疾病。已有研究表明，氧化应激和神经炎症是MS疾病进展的两个相互因果的因素。然而，氧化应激与神经炎症之间潜在的相互作用至今仍不清楚。通过对靶向脂质组学和转录组学的综合分析，我们的研究揭示了CNS脱髓鞘疾病中脂质代谢异常、线粒体功能障碍、氧化应激和神经炎症之间的潜在相互作用。本文的研究结果可能有助于确定CNS脱髓鞘疾病治疗的潜在靶点。
