Yun Hyung-Mun, Park Kyung-Ran, Kim Eun-Cheol, Hong Jin Tae
Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Dongdaemun-gu, Republic of Korea.
College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Oncotarget. 2015 Aug 28;6(25):20875-84. doi: 10.18632/oncotarget.5205.
Multiple sclerosis (MS) is a complex disease with an unknown etiology and has no effective medications despite extensive research. Antioxidants suppress oxidative damages which are implicated in the pathogenesis of MS. In this study, we showed that the expression of an antioxidant protein peroxiredoxin 6 (PRDX6) is markedly increased in spinal cord of mice with experimental autoimmune encephalomyelitis (EAE) compared to other PRDXs. PRDX6 transgenic (Tg) mice displayed a significant decrease in clinical severity and attenuated demyelination in EAE compared to wide type mice. The increased PRDX6 expression in astrocytes of EAE mice and MS patients reduced MMP9 expression, fibrinogen leakage, chemokines, and free radical stress, leading to reduction in blood-brain-barrier (BBB) disruption, peripheral immune cell infiltration, and neuroinflammation. Together, these findings suggest that PRDX6 expression may represent a therapeutic way to restrict inflammation in the central nervous system and potentiate oligodendrocyte survival, and suggest a new molecule for neuroprotective therapies in MS.
多发性硬化症（MS）是一种病因不明的复杂疾病，尽管进行了广泛研究，但仍没有有效的药物。抗氧化剂可抑制与MS发病机制相关的氧化损伤。在本研究中，我们发现与其他过氧化物酶相比，抗氧化蛋白过氧化物酶6（PRDX6）在实验性自身免疫性脑脊髓炎（EAE）小鼠脊髓中的表达显著增加。与野生型小鼠相比，PRDX6转基因（Tg）小鼠在EAE中的临床严重程度显著降低，脱髓鞘减轻。EAE小鼠和MS患者星形胶质细胞中PRDX6表达的增加降低了基质金属蛋白酶9（MMP9）的表达、纤维蛋白原渗漏、趋化因子和自由基应激，导致血脑屏障（BBB）破坏、外周免疫细胞浸润和神经炎症减少。总之，这些发现表明PRDX6表达可能是一种限制中枢神经系统炎症并增强少突胶质细胞存活的治疗方法，并为MS的神经保护治疗提出了一种新分子。
