Espinosa-Parrilla Yolanda, Gonzalez-Billault Christian, Fuentes Eduardo, Palomo Ivan, Alarcón Marcelo
School of Medicine, Universidad de Magallanes, Punta Arenas, Chile.
Laboratory of Molecular Medicine-LMM, Center for Education, Healthcare and Investigation-CADI, Universidad de Magallanes, Punta Arenas, Chile.
Front Aging Neurosci. 2019 Jul 2;11:151. doi: 10.3389/fnagi.2019.00151. eCollection 2019.
Platelets are anucleate cells that circulate in blood and are essential components of the hemostatic system. During aging, platelet numbers decrease and their aggregation capacity is reduced. Platelet dysfunctions associated with aging can be linked to molecular alterations affecting several cellular systems that include cytoskeleton rearrangements, signal transduction, vesicular trafficking, and protein degradation. Age platelets may adopt a phenotype characterized by robust secretion of extracellular vesicles that could in turn account for about 70-90% of blood circulating vesicles. Interestingly these extracellular vesicles are loaded with messenger RNAs and microRNAs that may have a profound impact on protein physiology at the systems level. Age platelet dysfunction is also associated with accumulation of reactive oxygen species. Thereby understanding the mechanisms of aging in platelets as well as their age-dependent dysfunctions may be of interest when evaluating the contribution of aging to the onset of age-dependent pathologies, such as those affecting the nervous system. In this review we summarize the findings that link platelet dysfunctions to neurodegenerative diseases including Alzheimer's Disease, Parkinson's Disease, Multiple Sclerosis, Huntington's Disease, and Amyotrophic Lateral Sclerosis. We discuss the role of platelets as drivers of protein dysfunctions observed in these pathologies, their association with aging and the potential clinical significance of platelets, and related miRNAs, as peripheral biomarkers for diagnosis and prognosis of neurodegenerative diseases.
血小板是循环于血液中的无核细胞，是止血系统的重要组成部分。在衰老过程中，血小板数量减少，其聚集能力降低。与衰老相关的血小板功能障碍可能与影响多个细胞系统的分子改变有关，这些系统包括细胞骨架重排、信号转导、囊泡运输和蛋白质降解。衰老的血小板可能呈现出一种以大量分泌细胞外囊泡为特征的表型，而这些细胞外囊泡反过来可能占循环血液中囊泡的70 - 90%。有趣的是，这些细胞外囊泡装载有信使核糖核酸和微小核糖核酸，它们可能在系统水平上对蛋白质生理学产生深远影响。衰老的血小板功能障碍还与活性氧的积累有关。因此，在评估衰老对诸如影响神经系统等与年龄相关疾病发病的贡献时，了解血小板衰老机制及其年龄依赖性功能障碍可能是有意义的。在这篇综述中，我们总结了将血小板功能障碍与神经退行性疾病联系起来的研究结果，这些疾病包括阿尔茨海默病、帕金森病、多发性硬化症、亨廷顿舞蹈症和肌萎缩侧索硬化症。我们讨论了血小板在这些疾病中观察到的蛋白质功能障碍驱动因素中的作用、它们与衰老的关联以及血小板和相关微小核糖核酸作为神经退行性疾病诊断和预后外周生物标志物的潜在临床意义。
