Duncan Greg J, Simkins Tyrell J, Emery Ben
Jungers Center for Neurosciences Research, Department of Neurology, Oregon Health & Science University, Portland, OR, United States.
Vollum Institute, Oregon Health & Science University, Portland, OR, United States.
Front Cell Dev Biol. 2021 Mar 8;9:653101. doi: 10.3389/fcell.2021.653101. eCollection 2021.
The myelination of axons by oligodendrocytes is a highly complex cell-to-cell interaction. Oligodendrocytes and axons have a reciprocal signaling relationship in which oligodendrocytes receive cues from axons that direct their myelination, and oligodendrocytes subsequently shape axonal structure and conduction. Oligodendrocytes are necessary for the maturation of excitatory domains on the axon including nodes of Ranvier, help buffer potassium, and support neuronal energy metabolism. Disruption of the oligodendrocyte-axon unit in traumatic injuries, Alzheimer's disease and demyelinating diseases such as multiple sclerosis results in axonal dysfunction and can culminate in neurodegeneration. In this review, we discuss the mechanisms by which demyelination and loss of oligodendrocytes compromise axons. We highlight the intra-axonal cascades initiated by demyelination that can result in irreversible axonal damage. Both the restoration of oligodendrocyte myelination or neuroprotective therapies targeting these intra-axonal cascades are likely to have therapeutic potential in disorders in which oligodendrocyte support of axons is disrupted.
少突胶质细胞对轴突的髓鞘形成是一种高度复杂的细胞间相互作用。少突胶质细胞与轴突存在相互的信号传导关系，其中少突胶质细胞接收来自轴突的信号，这些信号指导其髓鞘形成，随后少突胶质细胞塑造轴突结构和传导。少突胶质细胞对于轴突上兴奋性区域（包括郎飞结）的成熟是必需的，有助于缓冲钾离子，并支持神经元的能量代谢。在创伤性损伤、阿尔茨海默病以及诸如多发性硬化症等脱髓鞘疾病中，少突胶质细胞 - 轴突单元的破坏会导致轴突功能障碍，并最终导致神经退行性变。在本综述中，我们讨论了脱髓鞘和少突胶质细胞丢失损害轴突的机制。我们强调了由脱髓鞘引发的轴突内级联反应，这可能导致不可逆的轴突损伤。少突胶质细胞髓鞘形成的恢复或针对这些轴突内级联反应的神经保护疗法，在轴突的少突胶质细胞支持被破坏的疾病中可能都具有治疗潜力。
