| Background: Pakinsori?s Disease is the second most common and age-relatedneurodegenerative disorder in the world.The prevalence of PD is estimated at1% of people over 60 years old,and even 4-5% of people over 85 years old.PD diagnosis depends on clinical manifestation using Unified Pakinson's Disease Rating Scale and modified Hoehn-Yahr stage.PD clinical manifestation such as resting tremor,bradykinesia,cogwheel rigidity,and postural instability,doesn't appear until50%-70% dopaminergic neurons lost,making patients miss early diagnosis and treatment.MicroRNAs(mi RNAs)are small non-coding RNAs,which have been identified as post-transcriptional regulators by affecting mRNA translation and/or stability.In recent years,growing studies showed that mi RNAs participated in the development of Parkinson's disease,and some of the differentially expressed mi RNAs were helpful for the diagnosis of PD.But the results from different studies have also been different.That is related with the experimental methods,different research objects and different validation samples.The following two aspects are very important: 1 the blood component is complex and influence the stability of results;2,blood is lack of direct contact with brain.The discovery of exosomes provides convenience for solving this problem.Exosomes are membrane vesicles,a diameter of about 30-100 nm,secreted by many cells in physiological and pathological conditions,and exists in various body fluids.It is through the transfer of protein,lipid,DNA,mRNA and mi RNA and other substances to play a function.Recent studies have suggested that the exosomes may be transferred from the central nervous system through the blood brain barrier to the systemic circulation.This suggests that the miRNA of exosomes may be more realistic to reflect the intracranial conditions.Object: The aim of this study was to investigate the profile of miRNAs in plasma exosomes between patients with Pakinson's Disease and healthy donors and explore its clinical value as novel biomarkers for Pakinson's Disease.Methods: We collected serum samples of 51 sporadic PD patients and 50age/gender-matched healthy controls.Plasma exosomes were collected and identified by common methods.miRNAs of Plasma exosomes were analyzed by high-throughput sequencing followed by a qRT PCR assay.The qRT PCR assay was used to further confirm the expression of miRNAs screened by high-throughput sequencing.ROC curve analysis and clustering analysis determine the diagnostic usefulness of 6 selected miRNAs for PD.Results: We obtained particles with mode diameter <100nm and exosomal marker(CD63?Alix),defining as exosomes.High-throughput Sequencing showed169 miRNAs and 151 mi RNAs were detected in PD samples and control samples,respectively.We selected 12 miRNAs into further qRT-PCR assay then we identified six plasma exosomes miRNAs(hsa-miR-195,hsa-mi R-302 e,hsa-miR-15 b,hsa-miR-485-5p,hsa-miR-4483,hsa-miR-493-3p)that could distinguish 45 PD samples from 44 controls(p<0.01).hsa-miR-195 and hsa-miR-302 e were up-regulated and other four were down-regulated in the plasma exosomes of PD patients.Operating characteristic(ROC)curve analysis showed that this panel of six miRNAs can help diagnosis PD.Conclusions: The plasma exosomes of PD patients have rich and stable miRNAs,and its miRNA profile is different from healthy controls;In this study,we identified a profile of six plasma exosomes miRNAs,miR-195 and miRNA-302 e were up-regulated while miR-15 b,mi R-485-5p,miR-4483 and miR-493-3p were down-regulated.This six-miRNA group can be used as a potential biomarker for the diagnosis of PD. |
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