Gong Zhenxiang, Ba Li, Zhang Min
Department of Neurology and Psychiatry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
J Biomed Res. 2022 Aug 28;36(5):336-342. doi: 10.7555/JBR.36.20220009.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by irreversible deterioration of upper and lower motor neurons (MNs). Previously, studies on the involvement of glial cells in the pathogenic process of ALS have mainly revolved around astrocytes and microglia. And oligodendrocytes (OLs) have only recently been highlighted. Grey matter demyelination within the motor cortex and proliferation of the oligodendrocyte precursor cells (OPCs) was observed in ALS patients. The selective ablation of mutant SOD1 (the dysfunctional superoxide dismutase) from the oligodendrocyte progenitors after birth significantly delayed disease onset and prolonged the overall survival in ALS mice model (SOD1 ). In this study, we review the several mechanisms of oligodendrocyte dysfunction involved in the pathological process of myelin damage and MNs death during ALS. Particularly, we examined the insufficient local energy supply from OLs to axons, impaired differentiation from OPCs into OLs mediated by oxidative stress damage, and inflammatory injury to the OLs. Since increasing evidence depicted that ALS is not a disease limited to MNs damage, exploring the mechanisms by which oligodendrocyte dysfunction is involved in MNs death would contribute to a more comprehensive understanding of ALS and identifying potential drug targets.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征是上下运动神经元（MNs）发生不可逆的退化。此前，关于胶质细胞在ALS致病过程中的作用的研究主要围绕星形胶质细胞和小胶质细胞展开。而少突胶质细胞（OLs）直到最近才受到关注。在ALS患者中观察到运动皮层内的灰质脱髓鞘以及少突胶质前体细胞（OPCs）的增殖。出生后从少突胶质祖细胞中选择性剔除突变型SOD1（功能失调的超氧化物歧化酶）可显著延迟ALS小鼠模型（SOD1）的疾病发作并延长其总体生存期。在本研究中，我们综述了ALS过程中少突胶质细胞功能障碍参与髓鞘损伤和MNs死亡病理过程的几种机制。特别是，我们研究了少突胶质细胞向轴突提供的局部能量供应不足、氧化应激损伤介导的少突胶质前体细胞向少突胶质细胞分化受损以及少突胶质细胞的炎性损伤。由于越来越多的证据表明ALS并非仅限于MNs损伤的疾病，探索少突胶质细胞功能障碍参与MNs死亡的机制将有助于更全面地了解ALS并确定潜在的药物靶点。
