Martinez Bridget, Peplow Philip V
Physical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, USA; Department of Medicine, St. Georges University School of Medicine, Grenada.
Department of Anatomy, University of Otago, Dunedin, New Zealand.
Neural Regen Res. 2020 Oct;15(10):1831-1837. doi: 10.4103/1673-5374.280307.
Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain, spinal cord and optic nerve leading to demyelination. Focal demyelination is associated with relapsing-remitting multiple sclerosis, while progressive forms of the disease show axonal degeneration and neuronal loss. The tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and sensitivity. MicroRNAs (miRNAs) are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases. A review of recent studies with the experimental autoimmune encephalomyelitis animal model (mostly female mice 6-12 weeks of age) has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset (asymptomatic) stage when assessed in blood plasma and urine exosomes, and spinal cord tissue. The expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes, brain and spinal cord tissue, and at the post-peak (chronic) stage of experimental autoimmune encephalomyelitis disease in spinal cord tissue. Therapies using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis disease. Interestingly, experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a, miR-23b, miR-497, miR-26a, and miR-20b, or by suppression of miR-182, miR-181c, miR-223, miR-155, and miR-873. Further studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease course. Additionally, studies should be performed with male mice of a similar age, and with aged male and female mice.
多发性硬化症是一种中枢神经系统的自身免疫性神经退行性疾病，其特征是有明显的炎性浸润进入脑、脊髓和视神经，导致脱髓鞘。局灶性脱髓鞘与复发缓解型多发性硬化症相关，而该疾病的进展形式则表现为轴突变性和神经元丢失。目前用于多发性硬化症临床诊断和管理的检测方法由于特异性和敏感性存在局限性。微小RNA（miRNA）在包括脱髓鞘和神经炎性疾病在内的许多疾病和病症中表达失调。对近期使用实验性自身免疫性脑脊髓炎动物模型（大多为6至12周龄的雌性小鼠）的研究综述证实，miRNA作为实验性自身免疫性脑脊髓炎疾病的生物标志物，重要的是在血浆、尿液外泌体和脊髓组织中进行评估时，在发病前（无症状）阶段即可检测到。某些miRNA的表达在血浆、尿液外泌体、脑和脊髓组织中的疾病发作和高峰期以及实验性自身免疫性脑脊髓炎疾病的高峰期后（慢性）阶段的脊髓组织中也失调。发现使用miRNA模拟物或抑制剂的疗法可延迟诱导并减轻实验性自身免疫性脑脊髓炎疾病的严重程度。有趣的是，通过miR-146a、miR-23b、miR-497、miR-26a和miR-20b的过表达，或通过抑制miR-182、miR-181c、miR-223、miR-155和miR-873，实验性自身免疫性脑脊髓炎疾病的严重程度降低。有必要进一步研究以更全面地确定实验性自身免疫性脑脊髓炎动物血浆和尿液外泌体中的miRNA谱，因为它们可作为无症状多发性硬化症和疾病进程的生物标志物。此外，应使用年龄相似的雄性小鼠以及老年雄性和雌性小鼠进行研究。
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