Faculty of Human, Health, and Medical Science, Department of Clinical Medicine, Macquarie University, Wallumattagal Campus, Macquarie Park, NSW 2109, Australia.
Save Sight Institute, University of Sydney, 8 Macquarie St, Sydney, NSW 2000, Australia.
Rev Neurosci. 2023 Nov 22;35(3):271-292. doi: 10.1515/revneuro-2023-0081. Print 2024 Apr 25.
Myelination of axons in the central nervous system offers numerous advantages, including decreased energy expenditure for signal transmission and enhanced signal speed. The myelin sheaths surrounding an axon consist of a multi-layered membrane that is formed by oligodendrocytes, while specific glycoproteins and lipids play various roles in this formation process. As beneficial as myelin can be, its dysregulation and degeneration can prove detrimental. Inflammation, oxidative stress, and changes in cellular metabolism and the extracellular matrix can lead to demyelination of these axons. These factors are hallmark characteristics of certain demyelinating diseases including multiple sclerosis. The effects of demyelination are also implicated in primary degeneration in diseases such as glaucoma and Alzheimer's disease, as well as in processes of secondary degeneration. This reveals a relationship between myelin and secondary processes of neurodegeneration, including resultant degeneration following traumatic injury and transsynaptic degeneration. The role of myelin in primary and secondary degeneration is also of interest in the exploration of strategies and targets for remyelination, including the use of anti-inflammatory molecules or nanoparticles to deliver drugs. Although the use of these methods in animal models of diseases have shown to be effective in promoting remyelination, very few clinical trials in patients have met primary end points. This may be due to shortcomings or considerations that are not met while designing a clinical trial that targets remyelination. Potential solutions include diversifying disease targets and requiring concomitant interventions to promote rehabilitation.
中枢神经系统轴突的髓鞘形成有许多优点，包括降低信号传输的能量消耗和提高信号速度。围绕轴突的髓鞘由多层膜组成，由少突胶质细胞形成，而特定的糖蛋白和脂质在这个形成过程中发挥各种作用。髓鞘虽然有益，但它的失调和退化也可能是有害的。炎症、氧化应激以及细胞代谢和细胞外基质的变化可导致这些轴突脱髓鞘。这些因素是某些脱髓鞘疾病（如多发性硬化症）的标志性特征。脱髓鞘的影响也与青光眼和阿尔茨海默病等疾病的原发性变性以及继发性变性过程有关。这揭示了髓鞘与神经变性的继发性过程之间的关系，包括创伤后和突触间变性后的变性。髓鞘在原发性和继发性变性中的作用也引起了人们对髓鞘再生策略和靶点的兴趣，包括使用抗炎分子或纳米颗粒来输送药物。尽管这些方法在疾病的动物模型中已被证明能有效促进髓鞘再生，但在患者中进行的很少有临床试验达到主要终点。这可能是由于在设计针对髓鞘再生的临床试验时存在缺陷或未满足的考虑因素。潜在的解决方案包括多样化疾病靶点和需要伴随干预措施以促进康复。
