Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, 150080, Heilongjiang Province, China.
Department of Neurology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China.
Mol Neurobiol. 2024 Jun;61(6):3397-3408. doi: 10.1007/s12035-023-03773-2. Epub 2023 Nov 22.
Exosomes are nanoscale small vesicles (EVs) secreted by cells that carry important bio information, including proteins, miRNAs, and more. Exosome contents are readily present in body fluids, including blood, and urine of humans and animals, and thereby act as markers of diseases. In patients with Parkinson's disease (PD), exosomes may spread alpha-synuclein and miR-184 between the cells contributing to dopaminergic neuronal loss. In this study, we detected the levels of miR-184 in urine-excreted neuronal exosomes between PD patients and age-matched healthy subjects by qRT-PCR analysis. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were also used to determine the ultracellular structures of exosomes nanoparticles. MPP + and MPTP were used to construct the cell and animal PD model. Behavioral tests were used to detect motor performance. Furthermore, the cytological experiments were measured to examine the relationship between miR-184 and ZNF865. We found that the levels of miR-184 in urine-derived neuronal exosomes from PD patients were higher, compared to aged-matched normal people. The exosomes from PD patients were larger with greater numbers than those from the age-matched healthy subjects. The difference in miR-184 in urinary exosomes between PD patients and normal people may provide a novel perspective for early diagnosis of PD. However, no difference in CD63 level was observed in Exo-control and Exo-PD groups (exosome from control or PD groups). Moreover, ZNF865 was detected as the targeted gene of miR-184. In addition, miR-184 ASO (miR-184 antisense oligodeoxynucleotide, miR-184 ASO) could rescue the damage of neuronal apoptosis and motor performance in PD mice. Our results showed the miR-184 potential to function as a diagnostic marker of PD.
外泌体是细胞分泌的纳米级小囊泡 (EV)，携带包括蛋白质、miRNA 等在内的重要生物信息。外泌体内容物在人体和动物的体液中（包括血液和尿液）很容易被检测到，因此可作为疾病的标志物。在帕金森病 (PD) 患者中，外泌体可能在细胞之间传播α-突触核蛋白和 miR-184，从而导致多巴胺能神经元丧失。在这项研究中，我们通过 qRT-PCR 分析检测了 PD 患者和年龄匹配的健康受试者尿液中神经元来源的外泌体中的 miR-184 水平。还使用透射电子显微镜 (TEM) 和纳米颗粒跟踪分析 (NTA) 来确定外泌体纳米颗粒的细胞外结构。使用 MPP+和 MPTP 构建细胞和动物 PD 模型。使用行为测试来检测运动性能。此外，还进行了细胞学实验来检查 miR-184 和 ZNF865 之间的关系。我们发现，与年龄匹配的正常人相比，PD 患者尿液来源的神经元外泌体中的 miR-184 水平更高。与年龄匹配的健康受试者相比，来自 PD 患者的外泌体更大，数量更多。PD 患者和正常人尿液中外泌体 miR-184 的差异可能为 PD 的早期诊断提供新视角。然而，在 Exo-control 和 Exo-PD 组（对照或 PD 组来源的外泌体）中均未观察到 CD63 水平的差异。此外，还检测到 ZNF865 是 miR-184 的靶向基因。另外，miR-184 ASO（miR-184 反义寡核苷酸，miR-184 ASO）可以挽救 PD 小鼠神经元凋亡和运动性能的损伤。我们的结果表明，miR-184 有潜力成为 PD 的诊断标志物。
