脱髓鞘疾病通常由多种触发因素引起,包括免疫反应,病毒感染,营养不良,缺氧,或者遗传因素,所有这些都会导致神经系统中髓磷脂的丧失。髓鞘碎片在病变部位的积累导致神经炎症并抑制髓鞘再生;因此,及时清除髓鞘碎片至关重要。最初,细胞表面上的Fc和补体受体是负责去除髓鞘碎片的主要清除受体。然而,随后的研究揭示了额外受体的参与,包括Mac-2TAM受体,和低密度脂蛋白受体相关蛋白1,促进去除过程。除了小胶质细胞和巨噬细胞,作为疾病阶段的主要效应细胞,多种其他细胞类型,如星形胶质细胞,施万细胞,和血管内皮细胞已被证明参与吞噬髓鞘碎片。此外,我们得出结论,少突胶质细胞前体细胞,作为髓鞘形成前体细胞,也表现出这种吞噬能力。此外,我们的研究小组创新性地确定了低密度脂蛋白受体是髓鞘碎片的潜在吞噬受体.在这篇文章中,我们讨论了各种吞噬细胞在脱髓鞘疾病中的功能过程。我们还强调了由吞噬作用引发的信号通路的改变,并提供所涉及的各种吞噬受体的全面概述。这些见解对于通过靶向吞噬作用来确定用于治疗脱髓鞘疾病的潜在治疗策略是非常宝贵的。
Demyelinating diseases are often caused by a variety of triggers, including immune responses, viral infections, malnutrition, hypoxia, or genetic factors, all of which result in the loss of myelin in the nervous system. The accumulation of myelin debris at the lesion site leads to neuroinflammation and inhibits remyelination; therefore, it is crucial to promptly remove the myelin debris. Initially, Fc and complement
receptors on cellular surfaces were the primary clearance
receptors responsible for removing myelin debris. However, subsequent studies have unveiled the involvement of additional
receptors, including Mac-2, TAM
receptors, and the low-density lipoprotein receptor-related protein 1, in facilitating the removal process. In addition to microglia and macrophages, which serve as the primary effector cells in the disease phase, a variety of other cell types such as astrocytes, Schwann cells, and vascular endothelial cells have been demonstrated to engage in the phagocytosis of myelin debris. Furthermore, we have concluded that oligodendrocyte precursor cells, as myelination precursor cells, also exhibit this phagocytic capability. Moreover, our research group has innovatively identified the low-density lipoprotein receptor as a potential phagocytic receptor for myelin debris. In this article, we discuss the functional processes of various phagocytes in demyelinating diseases. We also highlight the alterations in signaling pathways triggered by phagocytosis, and provide a comprehensive overview of the various phagocytic
receptors involved. Such insights are invaluable for pinpointing potential therapeutic strategies for the treatment of demyelinating diseases by targeting phagocytosis.