Central nervous system-derived extracellular vesicles: the next generation of neural circulating biomarkers?

IF 10.8 1区 医学 Q1 NEUROSCIENCES Translational Neurodegeneration Pub Date : 2024-06-19 DOI:10.1186/s40035-024-00418-9
Rocío Del Carmen Bravo-Miana, Jone Karmele Arizaga-Echebarria, David Otaegui
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Abstract

The central nervous system (CNS) is integrated by glial and neuronal cells, and both release extracellular vesicles (EVs) that participate in CNS homeostasis. EVs could be one of the best candidates to operate as nanosized biological platforms for analysing multidimensional bioactive cargos, which are protected during systemic circulation of EVs. Having a window into the molecular level processes that are happening in the CNS could open a new avenue in CNS research. This raises a particular point of interest: can CNS-derived EVs in blood serve as circulating biomarkers that reflect the pathological status of neurological diseases? L1 cell adhesion molecule (L1CAM) is a widely reported biomarker to identify CNS-derived EVs in peripheral blood. However, it has been demonstrated that L1CAM is also expressed outside the CNS. Given that principal data related to neurodegenerative diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease were obtained using L1CAM-positive EVs, efforts to overcome present challenges related to its specificity are required. In this sense, other surface biomarkers for CNS-derived EVs, such as glutamate aspartate transporter (GLAST) and myelin oligodendrocyte glycoprotein (MOG), among others, have started to be used. Establishing a panel of EV biomarkers to analyse CNS-derived EVs in blood could increase the specificity and sensitivity necessary for these types of studies. This review covers the main evidence related to CNS-derived EVs in cerebrospinal fluid and blood samples of patients with neurological diseases, focusing on the reported biomarkers and the technical possibilities for their isolation. EVs are emerging as a mirror of brain physiopathology, reflecting both localized and systemic changes. Therefore, when the technical hindrances for EV research and clinical applications are overcome, novel disease-specific panels of EV biomarkers would be discovered to facilitate transformation from traditional medicine to personalized medicine.

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中枢神经系统源性细胞外囊泡:下一代神经循环生物标志物?
中枢神经系统(CNS)由神经胶质细胞和神经元细胞组成,这两种细胞都会释放参与中枢神经系统平衡的细胞外囊泡 (EV)。细胞外囊泡可以作为分析多维生物活性载体的纳米生物平台,是最佳候选者之一。有了了解中枢神经系统分子水平过程的窗口,就能为中枢神经系统研究开辟一条新途径。这引发了一个特别的兴趣点:血液中的中枢神经系统衍生 EV 能否作为循环生物标志物,反映神经系统疾病的病理状态?L1细胞粘附分子(L1CAM)是一种广泛报道的生物标记物,可用于识别外周血中中枢神经系统衍生的EV。然而,有研究表明,L1CAM 在中枢神经系统外也有表达。鉴于多发性硬化症、肌萎缩性脊髓侧索硬化症、帕金森病和阿尔茨海默病等神经退行性疾病的主要相关数据都是利用 L1CAM 阳性 EVs 获得的,因此需要努力克服目前与其特异性相关的挑战。从这个意义上说,其他中枢神经系统衍生EV的表面生物标记物,如谷氨酸天冬氨酸转运体(GLAST)和髓鞘少突胶质细胞糖蛋白(MOG)等,已开始被使用。建立一组 EV 生物标记物来分析血液中来源于中枢神经系统的 EV 可提高这类研究所需的特异性和灵敏度。本综述涵盖了与神经系统疾病患者脑脊液和血液样本中中枢神经系统衍生 EVs 有关的主要证据,重点是已报道的生物标记物及其分离技术的可能性。EVs 正在成为大脑生理病理的一面镜子,既能反映局部变化,也能反映全身变化。因此,当EV研究和临床应用的技术障碍被克服后,新的疾病特异性EV生物标记物就会被发现,从而促进从传统医学到个性化医学的转变。
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来源期刊
Translational Neurodegeneration
Translational Neurodegeneration Neuroscience-Cognitive Neuroscience
CiteScore
19.50
自引率
0.80%
发文量
44
审稿时长
10 weeks
期刊介绍: Translational Neurodegeneration, an open-access, peer-reviewed journal, addresses all aspects of neurodegenerative diseases. It serves as a prominent platform for research, therapeutics, and education, fostering discussions and insights across basic, translational, and clinical research domains. Covering Parkinson's disease, Alzheimer's disease, and other neurodegenerative conditions, it welcomes contributions on epidemiology, pathogenesis, diagnosis, prevention, drug development, rehabilitation, and drug delivery. Scientists, clinicians, and physician-scientists are encouraged to share their work in this specialized journal tailored to their fields.
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