Guo Min, Hao Yining, Feng Yiwei, Li Haiqing, Mao Yiting, Dong Qiang, Cui Mei
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.
Front Mol Neurosci. 2021 May 11;14:630808. doi: 10.3389/fnmol.2021.630808. eCollection 2021.
Microglia play an important role in neurodegenerative disease [i.e., Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS)]. These diseases share some similar pathological changes and several microglia-associated processes, including immune response, neuroinflammation, phagocytosis, elimination of synapses et al. Microglia in the central nervous system (CNS) has been described as having both destructive and protective effects in neurological disorders. Besides, considerable evidence also indicates that microglia play a significant role in neurogenesis, neuronal cell death, and synaptic interactions. The communication between microglia and neurons is of vital role in regulating complex functions which are key to appropriate the activity of the brain. Accumulating studies have also demonstrated that exosomes with sizes ranging from 40-100 nm, released by microglia, could serve as key mediators in intercellular signaling. These exosomes, identified in terms of cellular origin in many kinds of biological fluids, exert their effects by delivering specific cargos such as proteins, microRNAs (miRNAs), and mRNAs. It was shown that microglial exosomes could transport to and be uptake by neurons, which may either be beneficial or instead, detrimental to CNS diseases. The focus of this review is to summarize the involvement of microglial exosomes in critical pathologies associated with neurodegenerative disease and how they contribute to these disorders, including PD, AD, and ALS. We also review the application of microglia exosomes as potential biomarkers in monitoring disease progression, as well as focusing on their roles as drug delivery vehicles in treating neurodegenerative disorders.
小胶质细胞在神经退行性疾病[即帕金森病(PD)、阿尔茨海默病(AD)和肌萎缩侧索硬化症(ALS)]中发挥着重要作用。这些疾病具有一些相似的病理变化以及几种与小胶质细胞相关的过程,包括免疫反应、神经炎症、吞噬作用、突触消除等。中枢神经系统(CNS)中的小胶质细胞在神经疾病中被描述为具有破坏和保护两种作用。此外,大量证据还表明小胶质细胞在神经发生、神经元细胞死亡和突触相互作用中发挥着重要作用。小胶质细胞与神经元之间的通讯在调节复杂功能方面起着至关重要的作用,而这些复杂功能是大脑正常活动的关键。越来越多的研究还表明,小胶质细胞释放的大小在40 - 100纳米之间的外泌体可以作为细胞间信号传导的关键介质。这些在多种生物体液中根据细胞来源鉴定出的外泌体,通过传递特定的货物如蛋白质、微小RNA(miRNA)和信使RNA发挥作用。研究表明,小胶质细胞外泌体可以运输到神经元并被其摄取,这对中枢神经系统疾病可能是有益的,也可能是有害的。本综述的重点是总结小胶质细胞外泌体在与神经退行性疾病相关的关键病理过程中的参与情况,以及它们如何导致这些疾病,包括PD、AD和ALS。我们还综述了小胶质细胞外泌体作为潜在生物标志物在监测疾病进展中的应用,以及它们作为药物递送载体在治疗神经退行性疾病中的作用。