Gomes Dimitria E, Witwer Kenneth W
Cornell University College of Veterinary Medicine, Ithaca, New York, USA.
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Extracell Biol. 2022 Mar;1(3). doi: 10.1002/jex2.35. Epub 2022 Apr 5.
When released into biological fluids like blood or saliva, brain extracellular vesicles (EVs) might provide a window into otherwise inaccessible tissue, contributing useful biomarkers of neurodegenerative and other central nervous system (CNS) diseases. To enrich for brain EVs in the periphery, however, cell-specific EV surface markers are needed. The protein that has been used most frequently to obtain EVs of putative neuronal origin is the transmembrane L1 cell adhesion molecule (L1CAM/CD171). In this systematic review, we examine the existing literature on L1CAM and EVs, including investigations of both neurodegenerative disease and cancer through the lens of the minimal information for studies of EVs (MISEV), specifically in the domains of nomenclature usage, EV sources, and EV separation and characterization. Although numerous studies have reported L1CAM-associated biomarker signatures that correlate with disease, interpretation of these results is complicated since L1CAM expression is not restricted to neurons and is also upregulated during cancer progression. A recent study has suggested that L1CAM epitopes are present in biofluids mostly or entirely as cleaved, soluble protein. Our findings on practices and trends in L1CAM-mediated EV separation, enrichment, and characterization yield insights that may assist with interpreting results, evaluating rigor, and suggesting avenues for further exploration.
当释放到血液或唾液等生物流体中时，脑细胞外囊泡（EVs）可能为进入其他难以接近的组织提供一个窗口，有助于发现神经退行性疾病和其他中枢神经系统（CNS）疾病的有用生物标志物。然而，为了在外周血中富集脑源性EVs，需要细胞特异性的EV表面标志物。最常用于获取假定神经元来源的EVs的蛋白质是跨膜L1细胞粘附分子（L1CAM/CD171）。在本系统综述中，我们通过细胞外囊泡研究的最低信息标准（MISEV），审视了关于L1CAM和EVs的现有文献，包括对神经退行性疾病和癌症的研究，特别是在命名法使用、EV来源以及EV分离和表征等领域。尽管许多研究报告了与疾病相关的L1CAM相关生物标志物特征，但由于L1CAM的表达不仅限于神经元，而且在癌症进展过程中也会上调，这些结果的解释变得复杂。最近的一项研究表明，L1CAM表位在生物流体中大多或全部以裂解的可溶性蛋白形式存在。我们关于L1CAM介导的EV分离、富集和表征的实践与趋势的研究结果，为解释结果、评估严谨性以及提出进一步探索的途径提供了见解。
