Pegtel D M, Peferoen L, Amor S
Exosomes Research Group, VU University Medical Center, 1007 MB Amsterdam, The Netherlands
Neuropathology, Department of Pathology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
Philos Trans R Soc Lond B Biol Sci. 2014 Sep 26;369(1652). doi: 10.1098/rstb.2013.0516.
Homeostasis relies heavily on effective cell-to-cell communication. In the central nervous system (CNS), probably more so than in other organs, such communication is crucial to support and protect neurons especially during ageing, as well as to control inflammation, remove debris and infectious agents. Emerging evidence indicates that extracellular vesicles (EVs) including endosome-derived exosomes and fragments of the cellular plasma membrane play a key role in intercellular communication by transporting messenger RNA, microRNA (miRNA) and proteins. In neurodegenerative diseases, secreted vesicles not only remove misfolded proteins, but also transfer aggregated proteins and prions and are thus thought to perpetuate diseases by 'infecting' neighbouring cells with these pathogenic proteins. Conversely, in other CNS disorders signals from stressed cells may help control inflammation and inhibit degeneration. EVs may also reflect the status of the CNS and are present in the cerebrospinal fluid indicating that exosomes may act as biomarkers of disease. That extracellular RNA and in particular miRNA, can be transferred by EV also indicates that these vesicles could be used as carriers to specifically target the CNS to deliver immune modulatory drugs, neuroprotective agents and anti-cancer drugs. Here, we discuss the recent evidence indicating the potential role of exosomes in neurological disorders and how knowledge of their biology may enable a Trojan-horse approach to deliver drugs into the CNS and treat neurodegenerative and other disorders of the CNS.
内稳态在很大程度上依赖于有效的细胞间通讯。在中枢神经系统(CNS)中,这种通讯对于支持和保护神经元(尤其是在衰老过程中)以及控制炎症、清除碎片和病原体可能比在其他器官中更为关键。新出现的证据表明,包括内体衍生的外泌体和细胞质膜片段在内的细胞外囊泡(EVs)通过运输信使核糖核酸、微小核糖核酸(miRNA)和蛋白质在细胞间通讯中发挥关键作用。在神经退行性疾病中,分泌的囊泡不仅能清除错误折叠的蛋白质,还能转移聚集的蛋白质和朊病毒,因此被认为通过用这些致病蛋白质“感染”邻近细胞而使疾病持续存在。相反,在其他中枢神经系统疾病中,应激细胞发出的信号可能有助于控制炎症并抑制退化。细胞外囊泡也可能反映中枢神经系统的状态,并且存在于脑脊液中,这表明外泌体可能作为疾病的生物标志物。细胞外核糖核酸,尤其是微小核糖核酸能够通过细胞外囊泡转移,这也表明这些囊泡可以用作载体,特异性地靶向中枢神经系统以递送免疫调节药物、神经保护剂和抗癌药物。在此,我们讨论最近的证据,这些证据表明外泌体在神经系统疾病中的潜在作用,以及对其生物学特性的了解如何能够采用特洛伊木马方法将药物递送至中枢神经系统并治疗神经退行性疾病和其他中枢神经系统疾病。