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与帕金森病病理生理学相关的循环炎症 miRNA。

Circulating Inflammatory miRNAs Associated with Parkinson's Disease Pathophysiology.

机构信息

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.

出版信息

Biomolecules. 2020 Jun 23;10(6):945. doi: 10.3390/biom10060945.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, being largely characterized by motor features. MicroRNAs (miRNAs) are small non-coding RNAs, whose deregulation has been associated with neurodegeneration in PD. In this study, miRNAs targeting cell death and/or inflammation pathways were selected and their expression compared in the serum of PD patients and healthy controls. We used two independent cohorts (discovery and validation) of 20 idiopathic PD patients (iPD) and 20 healthy controls each. We also analyzed an additional group of 45 patients with a mutation in the leucine-rich repeat kinase 2 () gene (LRRK2-PD). miRNA expression was determined using Taqman qRT-PCR and their performance to discriminate between groups was assessed by receiver operating characteristic (ROC) curve analysis. We found miR-146a, miR-335-3p, and miR-335-5p downregulated in iPD and LRRK2-PD patients versus controls in both cohorts. In addition, miR-155 was upregulated in LRRK2-PD compared to iPD patients showing an appropriate value of area under the ROC curve (AUC 0.80) to discriminate between the two groups. In conclusion, our study identified a panel of inflammatory related miRNAs differentially expressed between PD patients and healthy controls that highlight key pathophysiological processes and may contribute to improve disease diagnosis.

摘要

帕金森病(PD)是全球第二大常见的神经退行性疾病,主要表现为运动特征。微小 RNA(miRNA)是小的非编码 RNA,其失调与 PD 中的神经变性有关。在这项研究中,选择了针对细胞死亡和/或炎症途径的 miRNA,并比较了 PD 患者和健康对照组血清中的表达。我们使用了两个独立的队列(发现和验证),每个队列包含 20 名特发性 PD 患者(iPD)和 20 名健康对照者。我们还分析了另外 45 名富含亮氨酸重复激酶 2 (LRRK2)基因突变患者(LRRK2-PD)的组。使用 Taqman qRT-PCR 测定 miRNA 表达,并通过接收者操作特征(ROC)曲线分析评估其区分组别的性能。我们发现,miR-146a、miR-335-3p 和 miR-335-5p 在 iPD 和 LRRK2-PD 患者与对照组的两个队列中均下调。此外,miR-155 在 LRRK2-PD 中上调,与 iPD 患者相比,ROC 曲线下面积(AUC)具有适当的值(0.80),可区分两组。总之,我们的研究确定了一组在 PD 患者和健康对照组之间表达不同的炎症相关 miRNA,突出了关键的病理生理过程,并可能有助于改善疾病诊断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/829f/7356527/79e5b624f417/biomolecules-10-00945-g001.jpg

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