Genomic and post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy.
EnGenome SRL, 27100 Pavia, Italy.
Int J Mol Sci. 2021 Mar 8;22(5):2737. doi: 10.3390/ijms22052737.
Identifying biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common and different miRNA signatures in plasma derived LEVs and SEVs of Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia (FTD) patients. LEVs and SEVs were isolated from plasma of patients and healthy volunteers (CTR) by filtration and differential centrifugation and RNA was extracted. Small RNAs libraries were carried out by Next Generation Sequencing (NGS). MiRNAs discriminate all NDs diseases from CTRs and they can provide a signature for each NDs. Common enriched pathways for SEVs were instead linked to ubiquitin mediated proteolysis and Toll-like receptor signaling pathways and for LEVs to neurotrophin signaling and Glycosphingolipid biosynthesis pathway. LEVs and SEVs are involved in different pathways and this might give a specificity to their role in the spreading of the disease. The study of common and different miRNAs transported by LEVs and SEVs can be of great interest for biomarker discovery and for pathogenesis studies in neurodegeneration.
鉴定生物标志物对于神经退行性疾病（NDs）的早期诊断至关重要。大细胞外囊泡（LEVs）和小细胞外囊泡（SEVs）是大小和生物学功能不同的细胞外囊泡（EVs），在血液中运输，它们可能是 NDs 的有效生物标志物。我们的研究目的是研究阿尔茨海默病（AD）、帕金森病（PD）、肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD）患者血浆衍生的 LEVs 和 SEVs 中常见和不同的 miRNA 特征。通过过滤和差速离心从患者和健康志愿者（CTR）的血浆中分离 LEVs 和 SEVs，并提取 RNA。通过下一代测序（NGS）进行小 RNA 文库构建。miRNAs 可区分所有 NDs 疾病与 CTRs，并且可以为每种 NDs 提供特征。SEVs 的常见富集途径与泛素介导的蛋白水解和 Toll 样受体信号通路有关，而 LEVs 则与神经营养因子信号和糖脂生物合成途径有关。LEVs 和 SEVs 参与不同的途径，这可能使其在疾病传播中的作用具有特异性。研究由 LEVs 和 SEVs 转运的常见和不同的 miRNAs 对于生物标志物的发现和神经退行性病变的发病机制研究具有重要意义。
