Oligodendrocytes (OLs), the myelin-generating cells of the central nervous system (CNS), are active players in shaping neuronal circuitry and function. It has become increasingly apparent that injury to cells within the OL lineage plays a central role in neurodegeneration. In this review, we focus primarily on three degenerative disorders in which white matter loss is well documented: Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). We discuss clinical data implicating white matter injury as a key feature of these disorders, as well as shared and divergent phenotypes between them. We examine the cellular and molecular mechanisms underlying the alterations to OLs, including chronic neuroinflammation, aggregation of proteins, lipid dysregulation, and organellar stress. Last, we highlight prospects for therapeutic intervention targeting the OL lineage to restore function.

少突胶质细胞 (OL) 是中枢神经系统 (CNS) 的髓鞘生成细胞，在塑造神经元回路和功能方面发挥着积极作用。越来越明显的是，OL 谱系内的细胞损伤在神经变性中起着核心作用。在这篇综述中，我们主要关注三种有充分记录的白质损失的退行性疾病：阿尔茨海默病（AD）、帕金森病（PD）和肌萎缩侧索硬化症（ALS）。我们讨论了表明白质损伤是这些疾病的关键特征的临床数据，以及它们之间共有和不同的表型。我们研究了 OL 改变的细胞和分子机制，包括慢性神经炎症、蛋白质聚集、脂质失调和细胞器应激。最后，我们强调了针对 OL 谱系恢复功能的治疗干预的前景。