Khan Naushad Ahmad, Asim Mohammad, El-Menyar Ayman, Biswas Kabir H, Rizoli Sandro, Al-Thani Hassan
Clinical Research, Trauma Surgery Section, Department of Surgery, Hamad General Hospital, Doha, Qatar.
Department of Clinical Medicine, Weill Cornell Medical College, Doha, Qatar.
Front Aging Neurosci. 2022 Oct 6;14:933434. doi: 10.3389/fnagi.2022.933434. eCollection 2022.
Developing effective disease-modifying therapies for neurodegenerative diseases (NDs) requires reliable diagnostic, disease activity, and progression indicators. While desirable, identifying biomarkers for NDs can be difficult because of the complex cytoarchitecture of the brain and the distinct cell subsets seen in different parts of the central nervous system (CNS). Extracellular vesicles (EVs) are heterogeneous, cell-derived, membrane-bound vesicles involved in the intercellular communication and transport of cell-specific cargos, such as proteins, Ribonucleic acid (RNA), and lipids. The types of EVs include exosomes, microvesicles, and apoptotic bodies based on their size and origin of biogenesis. A growing body of evidence suggests that intercellular communication mediated through EVs is responsible for disseminating important proteins implicated in the progression of traumatic brain injury (TBI) and other NDs. Some studies showed that TBI is a risk factor for different NDs. In terms of therapeutic potential, EVs outperform the alternative synthetic drug delivery methods because they can transverse the blood-brain barrier (BBB) without inducing immunogenicity, impacting neuroinflammation, immunological responses, and prolonged bio-distribution. Furthermore, EV production varies across different cell types and represents intracellular processes. Moreover, proteomic markers, which can represent a variety of pathological processes, such as cellular damage or neuroinflammation, have been frequently studied in neurotrauma research. However, proteomic blood-based biomarkers have short half-lives as they are easily susceptible to degradation. EV-based biomarkers for TBI may represent the complex genetic and neurometabolic abnormalities that occur post-TBI. These biomarkers are not caught by proteomics, less susceptible to degradation and hence more reflective of these modifications (cellular damage and neuroinflammation). In the current narrative and comprehensive review, we sought to discuss the contemporary knowledge and better understanding the EV-based research in TBI, and thus its applications in modern medicine. These applications include the utilization of circulating EVs as biomarkers for diagnosis, developments of EV-based therapies, and managing their associated challenges and opportunities.
开发针对神经退行性疾病（NDs）的有效疾病修饰疗法需要可靠的诊断、疾病活动和进展指标。虽然很理想，但由于大脑复杂的细胞结构以及中枢神经系统（CNS）不同部位存在的不同细胞亚群，识别NDs的生物标志物可能很困难。细胞外囊泡（EVs）是异质性的、细胞来源的、膜结合囊泡，参与细胞间通讯以及细胞特异性货物（如蛋白质、核糖核酸（RNA）和脂质）的运输。根据其大小和生物发生起源，EVs的类型包括外泌体、微囊泡和凋亡小体。越来越多的证据表明，通过EVs介导的细胞间通讯负责传播与创伤性脑损伤（TBI）和其他NDs进展相关的重要蛋白质。一些研究表明，TBI是不同NDs的危险因素。在治疗潜力方面，EVs优于其他合成药物递送方法，因为它们可以穿过血脑屏障（BBB）而不诱导免疫原性，影响神经炎症、免疫反应并延长生物分布。此外，EVs的产生因不同细胞类型而异，并代表细胞内过程。此外，蛋白质组学标志物可代表多种病理过程，如细胞损伤或神经炎症，在神经创伤研究中经常被研究。然而，基于血液的蛋白质组学生物标志物半衰期短，因为它们很容易降解。基于EVs的TBI生物标志物可能代表TBI后发生的复杂遗传和神经代谢异常。这些生物标志物无法通过蛋白质组学检测到，不易降解，因此更能反映这些修饰（细胞损伤和神经炎症）。在当前的叙述性和综合性综述中，我们试图讨论当代知识并更好地理解基于EVs的TBI研究，以及其在现代医学中的应用。这些应用包括利用循环EVs作为诊断生物标志物、开发基于EVs的疗法以及应对其相关挑战和机遇。
