摘要
背景:多发性硬化(MS)是最常见的慢性神经系统疾病之一,表现为中枢神经系统进行性脱髓鞘。MS发病的研究而从–缓解复发的病期的来临,这变得很明显,由于小胶质细胞的激活,在白质中神经炎症和脱髓鞘/髓鞘再生。随后的进展期伴随着严重的神经系统症状,脱髓鞘和神经退行性病变会扩散到灰质和白质。在这篇综述中,我们讨论一个可能的线粒体活性氧的作用(mtROS)在MS的发病机制,对一些靶向线粒体抗氧化剂mtROS产生和作用机制为MS治疗的潜在成分。 结果:在MS的早期阶段,mtROS刺激NLRP3炎症组,这是至关重要的,局部的炎性病变的形成。后来,mtROS导致血脑屏障破坏工业诱导炎症介质,其次是白细胞浸润。白细胞和活化的小胶质细胞产生的ROS促进线粒体功能障碍和少突胶质细胞死亡。在进步的阶段,神经退行性疾病,也取决于过度mtROS代。目前,只有少数免疫调节药物用于治疗MS。这些药物主要减少复发次数,但不能阻止MS进展。某些饮食和合成抗氧化剂有DEM组织在动物模型中的MS的令人鼓舞的结果,但均无效的完成临床试验。 结论:新的线粒体靶向抗氧化剂可能是很有前途的MS治疗方案的组成部分,因为它们可以在极低剂量和同时演示应用。表明抗炎和神经保护活动。
关键词: 多发性硬化症,少突胶质细胞、髓鞘脱失,炎性体,线粒体,活性氧,线粒体定位的抗氧化剂,保护。
Current Medicinal Chemistry
Title:Mitochondria-targeted Antioxidants as a Prospective Therapeutic Strategy for Multiple Sclerosis
Volume: 24 Issue: 19
关键词: 多发性硬化症,少突胶质细胞、髓鞘脱失,炎性体,线粒体,活性氧,线粒体定位的抗氧化剂,保护。
摘要: Background: Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing–remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/ remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter. In this review, we discuss a possible role of mitochondrial reactive oxygen species (mtROS) in MS pathogenesis, mechanisms of mtROS generation and effects of some mitochondria-targeted antioxidants as potential components of MS therapy.
Results: In the early phase of MS, mtROS stimulate NLRP3 inflammasomes, which is critical for the formation of local inflammatory lesions. Later, mtROS contribute to blood-brain barrier disruption induced by mediators of inflammation, followed by infiltration of leukocytes. ROS generated by leukocytes and activated microglia promote mitochondrial dysfunction and oligodendrocyte cell death. In the progressive phase, neurodegeneration also depends on excessive mtROS generation. Currently, only a few immunomodulatory drugs are approved for treatment of MS. These drugs mainly reduce the number of relapses but do not stop MS progression. Certain dietary and synthetic antioxidants have demonstrated encouraging results in animal models of MS but were ineffective in the completed clinical trials. Conclusion: Novel mitochondria-targeted antioxidants could be promising components of combined programs for MS therapy considering that they can be applied at extremely low doses and concurrently demonstrate anti-inflammatory and neuroprotective activities.Export Options
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Cite this article as:
Mitochondria-targeted Antioxidants as a Prospective Therapeutic Strategy for Multiple Sclerosis, Current Medicinal Chemistry 2017; 24 (19) . https://dx.doi.org/10.2174/0929867324666170316114452
DOI https://dx.doi.org/10.2174/0929867324666170316114452 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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