Ma Hongyue, Zhu Mingxia, Chen Mengjie, Li Xiuli, Feng Xinhong
Department of Neurology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, China.
Biomark Res. 2024 Aug 13;12(1):81. doi: 10.1186/s40364-024-00624-7.
Tissue-resident macrophages and recruited macrophages play pivotal roles in innate immunity and the maintenance of brain homeostasis. Investigating the involvement of these macrophage populations in eliciting pathological changes associated with neurodegenerative diseases has been a focal point of research. Dysregulated states of macrophages can compromise clearance mechanisms for pathological proteins such as amyloid-β (Aβ) in Alzheimer's disease (AD) and TDP-43 in Amyotrophic lateral sclerosis (ALS). Additionally, recent evidence suggests that abnormalities in the peripheral clearance of pathological proteins are implicated in the pathogenesis and progression of neurodegenerative diseases. Furthermore, numerous genome-wide association studies have linked genetic risk factors, which alter the functionality of various immune cells, to the accumulation of pathological proteins. This review aims to unravel the intricacies of macrophage biology in both homeostatic conditions and neurodegenerative disorders. To this end, we initially provide an overview of the modifications in receptor and gene expression observed in diverse macrophage subsets throughout development. Subsequently, we outlined the roles of resident macrophages and recruited macrophages in neurodegenerative diseases and the progress of targeted therapy. Finally, we describe the latest advances in macrophage imaging methods and measurement of inflammation, which may provide information and related treatment strategies that hold promise for informing the design of future investigations and therapeutic interventions.
组织驻留巨噬细胞和募集的巨噬细胞在先天免疫和脑稳态维持中发挥关键作用。研究这些巨噬细胞群体在引发与神经退行性疾病相关的病理变化中的作用一直是研究的重点。巨噬细胞的失调状态会损害阿尔茨海默病（AD）中淀粉样β蛋白（Aβ）和肌萎缩侧索硬化症（ALS）中TDP-43等病理蛋白的清除机制。此外，最近的证据表明，病理蛋白外周清除异常与神经退行性疾病的发病机制和进展有关。此外，大量全基因组关联研究已将改变各种免疫细胞功能的遗传风险因素与病理蛋白的积累联系起来。本综述旨在揭示巨噬细胞生物学在稳态条件和神经退行性疾病中的复杂性。为此，我们首先概述了在发育过程中不同巨噬细胞亚群中观察到的受体和基因表达的变化。随后，我们概述了驻留巨噬细胞和募集的巨噬细胞在神经退行性疾病中的作用以及靶向治疗的进展。最后，我们描述了巨噬细胞成像方法和炎症测量的最新进展，这可能提供有前景的信息和相关治疗策略，为未来研究和治疗干预的设计提供参考。
