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血清和外泌体 miR-7-1-5p 和 miR-223-3p 作为帕金森病的潜在生物标志物。

Serum and Exosomal miR-7-1-5p and miR-223-3p as Possible Biomarkers for Parkinson's Disease.

机构信息

IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy.

Department of Pathophysiology and Transplantation, University of Milan, 20100 Milan, Italy.

出版信息

Biomolecules. 2023 May 19;13(5):865. doi: 10.3390/biom13050865.

DOI:10.3390/biom13050865
PMID:37238734
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10216839/
Abstract

The etiology of Parkinson's disease (PD) is poorly understood, and is strongly suspected to include both genetic and environmental factors. In this context, it is essential to investigate possible biomarkers for both prognostic and diagnostic purposes. Several studies reported dysregulated microRNA expression in neurodegenerative disorders, including PD. Using ddPCR, we investigated the concentrations of miR-7-1-5p, miR-499-3p, miR-223-3p and miR-223-5p-miRNAs involved in the α-synuclein pathway and in inflammation-in the serum and serum-isolated exosomes of 45 PD patients and 49 age- and sex-matched healthy controls (HC). While miR-499-3p and miR-223-5p showed no differences (1), serum concentration of miR-7-1-5p was significantly increased ( = 0.0007 vs. HC) and (2) miR-223-3p serum ( = 0.0006) and exosome ( = 0.0002) concentrations were significantly increased. ROC curve analysis showed that miR-223-3p and miR-7-1-5p serum concentration discriminates between PD and HC ( = 0.0001, in both cases). Notably, in PD patients, both miR-223-3p serum ( = 0.0008) and exosome ( = 0.006) concentrations correlated with levodopa equivalent daily dosage (LEDD). Finally, serum α-synuclein was increased in PD patients compared to HC ( = 0.025), and in patients correlated with serum miR-7-1-5p in ( = 0.05). Our results suggest that both miR-7-1-5p and miR-223-3p, distinguishing PD from HC, have the potential to be useful and non-invasive biomarkers in Parkinson's disease.

摘要

帕金森病 (PD) 的病因尚不清楚,强烈怀疑包括遗传和环境因素。在这种情况下,调查预后和诊断目的的可能生物标志物至关重要。几项研究报告称,在包括 PD 在内的神经退行性疾病中存在 miRNA 表达失调。使用 ddPCR,我们研究了血清和血清分离的外泌体中与 α-突触核蛋白途径和炎症相关的 miR-7-1-5p、miR-499-3p、miR-223-3p 和 miR-223-5p 的浓度在 45 名 PD 患者和 49 名年龄和性别匹配的健康对照者 (HC) 中。miR-499-3p 和 miR-223-5p 没有差异 (1),而血清 miR-7-1-5p 浓度显著升高 ( = 0.0007 与 HC 相比) 和 (2)miR-223-3p 血清 ( = 0.0006) 和外泌体 ( = 0.0002) 浓度均显著升高。ROC 曲线分析表明,miR-223-3p 和 miR-7-1-5p 血清浓度可区分 PD 和 HC ( = 0.0001,两种情况)。值得注意的是,在 PD 患者中,miR-223-3p 血清 ( = 0.0008) 和外泌体 ( = 0.006) 浓度与左旋多巴等效日剂量 (LEDD) 相关。最后,与 HC 相比,PD 患者的血清 α-突触核蛋白增加 ( = 0.025),且与血清 miR-7-1-5p 相关 ( = 0.05)。我们的结果表明,miR-7-1-5p 和 miR-223-3p 可将 PD 与 HC 区分开来,它们有可能成为帕金森病有用且非侵入性的生物标志物。

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