Smith J A, Leonardi T, Huang B, Iraci N, Vega B, Pluchino S
Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, UK.
Biogerontology. 2015 Apr;16(2):147-85. doi: 10.1007/s10522-014-9510-7. Epub 2014 Jun 28.
Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs-or specific EV cargoes-are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases.
多细胞生物依赖于多样且复杂的细胞间通讯网络来进行无数的生理过程。这些过程的破坏与疾病和功能紊乱的发生及传播有关，包括细胞和机体水平的衰老机制。近年来，分泌型细胞外囊泡（EVs）已被确定为一种特别新颖的细胞间通讯载体。EVs在局部和全身水平上在细胞间主动且特异性地运输生物活性蛋白、核酸和代谢物，在稳态和病理条件下以双向方式调节细胞反应。EVs不仅与一般的衰老过程有关，还被认为是包括癌症、神经退行性疾病等多种与年龄相关疾病的病理载体。因此，循环EVs或特定的EV货物正被用作疾病的假定生物标志物。另一方面，EVs作为多能生物活性物质的靶向细胞间穿梭载体，已显示出有前景的治疗特性，通过细胞工程有可能对其进行调节和增强。此外，人们对采用纳米医学方法通过使用合成类似物进行靶向药物递送来模拟EVs的假定治疗特性有着浓厚兴趣。在此，我们描述了关于EVs的起源和性质的已知信息，随后综述了它们在生物学和医学中的假定作用（包括合成EV类似物的使用），特别关注它们在衰老和与年龄相关的脑部疾病中的作用。
