Kent Sarah A, Miron Veronique E
UK Dementia Research Institute at The University of Edinburgh, Edinburgh, UK.
Centre for Discovery Brain Sciences, Chancellor's Building, The University of Edinburgh, Edinburgh, UK.
Nat Rev Immunol. 2024 Jan;24(1):49-63. doi: 10.1038/s41577-023-00907-4. Epub 2023 Jul 14.
Microglia are resident macrophages of the central nervous system that have key functions in its development, homeostasis and response to damage and infection. Although microglia have been increasingly implicated in contributing to the pathology that underpins neurological dysfunction and disease, they also have crucial roles in neurological homeostasis and regeneration. This includes regulation of the maintenance and regeneration of myelin, the membrane that surrounds neuronal axons, which is required for axonal health and function. Myelin is damaged with normal ageing and in several neurodegenerative diseases, such as multiple sclerosis and Alzheimer disease. Given the lack of approved therapies targeting myelin maintenance or regeneration, it is imperative to understand the mechanisms by which microglia support and restore myelin health to identify potential therapeutic approaches. However, the mechanisms by which microglia regulate myelin loss or integrity are still being uncovered. In this Review, we discuss recent work that reveals the changes in white matter with ageing and neurodegenerative disease, how this relates to microglia dynamics during myelin damage and regeneration, and factors that influence the regenerative functions of microglia.
小胶质细胞是中枢神经系统中的常驻巨噬细胞,在其发育、体内平衡以及对损伤和感染的反应中发挥着关键作用。尽管越来越多的研究表明小胶质细胞参与了导致神经功能障碍和疾病的病理过程,但它们在神经体内平衡和再生中也起着至关重要的作用。这包括对髓鞘(围绕神经元轴突的膜)的维持和再生的调节,而髓鞘对于轴突的健康和功能是必需的。随着正常衰老以及在一些神经退行性疾病(如多发性硬化症和阿尔茨海默病)中,髓鞘会受到损伤。鉴于缺乏针对髓鞘维持或再生的获批疗法,了解小胶质细胞支持和恢复髓鞘健康的机制以确定潜在的治疗方法势在必行。然而,小胶质细胞调节髓鞘损失或完整性的机制仍在不断被揭示。在这篇综述中,我们讨论了最近的研究工作,这些工作揭示了随着衰老和神经退行性疾病白质的变化、这与髓鞘损伤和再生过程中小胶质细胞动态变化的关系,以及影响小胶质细胞再生功能的因素。