Rashidbenam Zahra, Ozturk Ezgi, Pagnin Maurice, Theotokis Paschalis, Grigoriadis Nikolaos, Petratos Steven
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.
Laboratory of Experimental Neurology and Neuroimmunology, Department of Neurology, AHEPA University Hospital, Thessaloniki, Greece.
Front Cell Neurosci. 2023 Jun 8;17:1197492. doi: 10.3389/fncel.2023.1197492. eCollection 2023.
Multiple sclerosis (MS) can progress with neurodegeneration as a consequence of chronic inflammatory mechanisms that drive neural cell loss and/or neuroaxonal dystrophy in the central nervous system. Immune-mediated mechanisms can accumulate myelin debris in the disease extracellular milieu during chronic-active demyelination that can limit neurorepair/plasticity and experimental evidence suggests that potentiated removal of myelin debris can promote neurorepair in models of MS. The myelin-associated inhibitory factors (MAIFs) are integral contributors to neurodegenerative processes in models of trauma and experimental MS-like disease that can be targeted to promote neurorepair. This review highlights the molecular and cellular mechanisms that drive neurodegeneration as a consequence of chronic-active inflammation and outlines plausible therapeutic approaches to antagonize the MAIFs during the evolution of neuroinflammatory lesions. Moreover, investigative lines for translation of targeted therapies against these myelin inhibitors are defined with an emphasis on the chief MAIF, Nogo-A, that may demonstrate clinical efficacy of neurorepair during progressive MS.
多发性硬化症（MS）可因慢性炎症机制导致神经退行性变，这些机制会促使中枢神经系统中的神经细胞丢失和/或神经轴突营养不良。在慢性活动性脱髓鞘过程中，免疫介导的机制可在疾病的细胞外环境中积累髓鞘碎片，这会限制神经修复/可塑性，实验证据表明，在MS模型中增强髓鞘碎片的清除可促进神经修复。髓鞘相关抑制因子（MAIFs）是创伤模型和实验性MS样疾病中神经退行性过程的重要促成因素，可作为促进神经修复的靶点。本综述重点介绍了慢性活动性炎症导致神经退行性变的分子和细胞机制，并概述了在神经炎性病变发展过程中拮抗MAIFs的合理治疗方法。此外，还确定了针对这些髓鞘抑制剂的靶向治疗的转化研究方向，重点关注主要的MAIF，即Nogo-A，它可能在进展性MS期间展现出神经修复的临床疗效。
