线粒体靶向抗氧化剂治疗多发性硬化症的前瞻性治疗策略

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.

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