Departamento de Bioquimica y Biologia Molecular, Instituto de Neurociencias de Castilla y Leon (INCYL), Universidad de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Salamanca, Spain.
Curr Pharm Des. 2021 Oct 5;27(30):3273-3280. doi: 10.2174/1381612827666210127121829.
Mammalian nervous systems depend crucially on myelin sheaths covering the axons. In the central nervous system, myelin sheaths consist of lipid structures that are generated from the membrane of oligodendrocytes (OL). These sheaths allow fast nerve transmission, protect axons and provide them metabolic support. In response to specific traumas or pathologies, these lipid structures can be destabilized and generate demyelinating lesions. Multiple sclerosis (MS) is an example of a demyelinating disease in which the myelin sheaths surrounding the nerve fibers of the brain and spinal cord are damaged. MS is the leading cause of neurological disability in young adults in many countries, and its incidence has been increasing in recent decades. Related to its etiology, it is known that MS is an autoimmune and inflammatory CNS disease. However, there are no effective treatments for this disease and the immunomodulatory therapies that currently exist have proven limited success since they only delay the progress of the disease. Nowadays, one of the main goals in MS research is to find treatments which allow the recovery of neurological disabilities due to demyelination. To this end, different approaches, such as modulating intracellular signaling or regulating the lipid metabolism of OLs, are being considered. Here, in addition to immunosuppressive or immunomodulatory drugs that reduce the immune response against myelin sheaths, we review a diverse group of drugs that promotes endogenous remyelination in MS patients and their use may be interesting as potential therapeutic agents in MS disease. To this end, we compile specific treatments against MS that are currently in the market with remyelination strategies that have entered into human clinical trials for future reparative MS therapies. The method used in this study is a systematic literature review on PubMed, Web of Science and Science Direct databases up to May 31, 2020. To narrow down the search results in databases, more specific keywords, such as "myelin sheath", "remyelination", "demyelination", "oligodendrocyte" and "lipid synthesis" were used to focus the search. We preferred papers published after January 2015, but did not exclude earlier seminal papers.
哺乳动物的神经系统严重依赖于覆盖轴突的髓鞘。在中枢神经系统中，髓鞘由源自少突胶质细胞（OL）膜的脂质结构组成。这些鞘允许快速的神经传递，保护轴突并为其提供代谢支持。在特定的创伤或病理条件下，这些脂质结构可能会不稳定并产生脱髓鞘病变。多发性硬化症（MS）就是一个脱髓鞘疾病的例子，其中围绕脑和脊髓神经纤维的髓鞘被破坏。MS 是许多国家中导致年轻人神经功能障碍的主要原因，而且近年来其发病率一直在上升。与它的病因有关，已知 MS 是一种自身免疫性和炎症性中枢神经系统疾病。然而，目前还没有有效的治疗方法，现有的免疫调节疗法已经证明效果有限，因为它们只能延缓疾病的进展。如今，MS 研究的主要目标之一是寻找能够恢复脱髓鞘引起的神经功能障碍的治疗方法。为此，正在考虑多种方法，例如调节细胞内信号或调节 OL 的脂质代谢。在这里，除了减少针对髓鞘的免疫反应的免疫抑制或免疫调节药物外，我们还回顾了一组促进 MS 患者内源性髓鞘再生的不同药物，它们的使用可能作为 MS 疾病的潜在治疗药物很有意义。为此，我们编译了目前市场上针对 MS 的特定治疗方法，以及已经进入人类临床试验的髓鞘再生策略，作为未来修复性 MS 治疗的候选药物。本研究采用的方法是对截至 2020 年 5 月 31 日在 PubMed、Web of Science 和 Science Direct 数据库中进行的系统文献综述。为了缩小数据库中的搜索结果，使用了更具体的关键词，如“髓鞘”、“髓鞘再生”、“脱髓鞘”、“少突胶质细胞”和“脂质合成”，以集中搜索。我们更喜欢发表在 2015 年以后的论文，但不排除更早的重要论文。
