scholarly journals Profiling of Differentially Expressed MicroRNAs in Saliva of Parkinson's Disease Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanyan Jiang ◽  
Jing Chen ◽  
Yunchuang Sun ◽  
Fan Li ◽  
Luhua Wei ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Microarray Analysis ◽  
Target Genes ◽  
Characteristic Curve ◽  
Differentially Expressed ◽  
Diagnostic Efficacy ◽  
Mirna Microarray ◽  
Candidate Mirnas ◽  
Diagnostic Potential

Objective: This study aims to identify differentially expressed salivary miRNAs and validate the diagnostic potential for idiopathic Parkinson's disease (PD). Also, the disease specificity of candidate miRNAs was evaluated between PD, multiple system atrophy (MSA), and essential tremor (ET).Methods: We collected salivary samples from 50 PD, 20 ET, and 20 MSA patients, as well as 30 healthy controls (HCs). In the discovery phase, salivary miRNA microarray analysis was performed. In-silico analysis was used to investigate the target genes of differentially expressed miRNAs and clustered pathways. In validation phase, RT-qPCR was performed with samples from 30 PD patients and 30 HCs. Subsequently, we investigated candidate miRNAs in all recruited subjects. Receiver operating characteristic curve and Spearman correlation analysis was performed to determine diagnostic usefulness.Results: We identified 43 miRNAs that were differentially expressed between 5 PD patients and 5 HCs by miRNA microarray analysis. Computational analysis revealed the target genes were clustered in the pathways associated with ubiquitin protein ligase activity. The result of RT-qPCR showed that the miR-29a-3p and miR-29c-3p were found to be significantly downregulated (p = 0.004, p = 0.027), whereas the miR-6756-5p was significantly upregulated in 30 PD patients compared with 30 HCs (p = 0.032). The miR-29a-3p expression level in PD patients was significantly lower than ET patients (p = 0.035), but higher than MSA patients (p < 0.0001). The diagnostic efficacy reached a little higher when the combination of miR-29a-3p and miR-29c-3p.Conclusion: The miRNA combination of salivary miR-29a-3p and miR-29c-3p has potential to be a diagnostic biomarker for idiopathic PD.

Validation of Differentially Expressed Brain-Enriched microRNAs in the Plasma of Parkinson’s Disease Patients

2020 ◽  
Author(s):  
Stylianos Ravanidis ◽  
Anastasia Bougea ◽  
Nikolaos Papagiannakis ◽  
Christos Koros ◽  
Athina Simitsi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factor ◽  
Protein Modification ◽  
Differentially Expressed ◽  
Molecular Pathways ◽  
Healthy Controls ◽  
Neuron Development ◽  
Go Annotation ◽  
Diagnostic Potential

Abstract Background There is a pressing need to identify and validate, minimally invasive, molecular biomarkers that will complement current practices and increase the diagnostic accuracy in Parkinson’s disease (PD). Brain-enriched miRNAs regulate all aspects of neuron development and function; importantly, they are secreted by neurons in amounts that can be readily detected in the plasma. Τhe aim of the present study was to validate a set of previously identified brain-enriched miRNAs with a diagnostic potential for idiopathic PD and recognize the molecular pathways affected by these deregulated miRNAs.Methods RT-qPCR was performed in the plasma of 92 healthy controls and 108 idiopathic PD subjects. Statistical and in silico analyses were used to validate deregulated miRNAs and pathways in PD, respectively.Results miR-22-3p, miR-124-3p, miR-136-3p, miR-154-5p and miR-323a-3p levels were found to be differentially expressed between healthy controls and PD patients. miR-330-5p, miR-433-3p and miR-495-3p levels were overall higher in male subjects. Most of these miRNAs are clustered at Chr14q32 displaying CREB1, CEBPB, and MAZ transcription factor binding sites. Gene Ontology (GO) annotation analysis of deregulated miRNA targets revealed that ‘Protein modification’, ‘Transcription factor activity’ and ‘Cell death’ terms were over-represented. Kyoto Encyclopedia of Genes and Genome (KEGG) analysis revealed that ‘Long-term depression’, ‘TGF-beta signaling’, and ‘FoxO signaling’ pathways were significantly affected.Conclusions We validated a panel of brain-enriched miRNAs that can be used along with other measures for the detection of PD, revealed molecular pathways targeted by these deregulated miRNAs, and identified upstream transcription factors that may be directly implicated in their regulation and thereafter PD pathogenesis.

scholarly journals Transcriptomic Profiling of Circular RNA in Different Brain Regions of Parkinson’s Disease in a Mouse Model

2020 ◽  
Vol 21 (8) ◽  
pp. 3006 ◽  
Author(s):  
Erteng Jia ◽  
Ying Zhou ◽  
Zhiyu Liu ◽  
Liujing Wang ◽  
Tinglan Ouyang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Signaling Pathway ◽  
Target Genes ◽  
Kegg Pathway ◽  
Brain Regions ◽  
Differentially Expressed ◽  
Sequencing Analysis ◽  
Qrt Pcr

Parkinson’s disease (PD) is the second most common neurodegenerative disease and although many studies have been done on this disease, the underlying mechanisms are still poorly understood and further studies are warranted. Therefore, this study identified circRNA expression profiles in the cerebral cortex (CC), hippocampus (HP), striatum (ST), and cerebellum (CB) regions of the 1-methyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model using RNA sequencing (RNA-seq), and differentially expressed circRNA were validated using reverse transcription quantitative real-time PCR (qRT-PCR). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and competing endogenous RNA (ceRNA) network analyses were also performed to explore the potential function of circRNAs. The results show that, compared with the control group, 24, 66, 71, and 121 differentially expressed circRNAs (DE-circRNAs) were found in the CC, HP, ST, and CB, respectively. PDST vs. PDCB, PDST vs. PDHP, and PDCB vs. PDHP groups have 578, 110, and 749 DE-circRNAs, respectively. Then, seven DE-cirRNAs were selected for qRT-PCR verification, where the expressions were consistent with the sequencing analysis. The GO and KEGG pathway analyses revealed that these DE-circRNAs participate in several biological functions and signaling pathways, including glutamic synapse, neuron to neuron synapse, cell morphogenesis involved in neuron differentiation, Parkinson’s disease, axon guidance, cGMP-PKG signaling pathway, and PI3K-Akt signaling pathway. Furthermore, the KEGG analysis of the target genes predicted by DE-circRNAs indicated that the target genes predicted by mmu_circRNA_0003292, mmu_circRNA_0001320, mmu_circRNA_0005976, and mmu_circRNA_0005388 were involved in the PD-related pathway. Overall, this is the first study on the expression profile of circRNAs in the different brain regions of PD mouse model. These results might facilitate our understanding of the potential roles of circRNAs in the pathogenesis of PD. Moreover, the results also indicate that the mmu_circRNA_0003292-miRNA-132-Nr4a2 pathway might be involved in the regulation of the molecular mechanism of Parkinson’s disease.

scholarly journals Meta-analyses identify differentially expressed microRNAs in Parkinson’s disease

2018 ◽  
Author(s):  
Jessica Schulz ◽  
Petros Takousis ◽  
Inken Wohlers ◽  
Ivie O G Itua ◽  
Valerija Dobricic ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Differential Expression ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Microrna Expression ◽  
Differentially Expressed ◽  
Significant Differential Expression ◽  
Expression Studies ◽  
Meta Analyses

ABSTRACTObjectiveMicroRNA-mediated (dys)regulation of gene expression has been implicated in Parkinson’s disease (PD), although results of microRNA expression studies remain inconclusive. We aimed to identify microRNAs that show consistent differential expression across all published expression studies in PD.MethodsWe performed a systematic literature search on microRNA expression studies in PD and extracted data from eligible publications. After stratification for brain, blood, and cerebrospinal fluid (CSF)-derived specimen we performed meta-analyses across microRNAs assessed in three or more independent datasets. Meta-analyses were performed using effect-size and p-value based methods, as applicable.ResultsAfter screening 599 publications we identified 47 datasets eligible for meta-analysis. On these, we performed 160 meta-analyses on microRNAs quantified in brain (n=125), blood (n=31), or CSF samples (n=4). Twenty-one meta-analyses were performed using effect sizes. We identified 13 significantly (Bonferroni-adjusted α=3.13×10-4) differentially expressed microRNAs in brain (n=3) and blood (n=10) with consistent effect directions across studies. The most compelling findings were with hsa-miR-132-3p (p=6.37×10-5), hsa-miR-497-5p (p=1.35×10-4), and hsa-miR-133b (p=1.90×10-4) in brain, and with hsa-miR-221-3p (p=4.49×10-35), hsa-miR-214-3p (p=2.00×10-34), and hsa-miR-29c-3p (p=3.00×10-12) in blood. No significant signals were found in CSF. Analyses of GWAS data for target genes of brain microRNAs showed significant association (α=9.40×10-5) of genetic variants in nine loci.InterpretationWe identified several microRNAs that showed highly significant differential expression in PD. Future studies may assess the possible role of the identified brain miRNAs in pathogenesis and disease progression as well as the potential of the top blood microRNAs as biomarkers for diagnosis, progression or prediction of PD.

A Comparative Study of the Diagnostic Potential of Plasma and Erythrocytic α-Synuclein in Parkinson’s Disease

2019 ◽  
Vol 19 (5-6) ◽  
pp. 204-210
Author(s):  
Luxuan Wang ◽  
Guowei Wang ◽  
Yangyang Duan ◽  
Feng Wang ◽  
Shaoqing Lin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Predictive Power ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Expression Level ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Subjects ◽  
Diagnostic Potential

Background: Parkinson’s disease (PD) is a neurodegenerative disease characterized by intracellular α-synuclein (α-Syn) deposition. Alternation of the α-Syn expression level in plasma or erythrocytes may be used as a potential PD biomarker. However, no studies have compared their prognostic value directly with the same cohort. Methods: The levels of α-Syn in plasma and erythrocytes, obtained from 45 PD patients and 45 control subjects, were measured with enzyme-linked immunosorbent assay. Then, correlation and receiver operating characteristic curve (ROC) analysis were performed to characterize the predictive power of erythrocytic and plasma α-Syn. Results: Our results showed that α-Syn expression levels in both plasma and erythrocytes were significantly higher in PD patients than in control subjects (823.14 ± 257.79 vs. 297.10 ± 192.82 pg/mL, p < 0.0001 in plasma; 3,104.14 ± 143.03 vs. 2,944.82 ± 200.41 pg/mL, p < 0.001 in erythrocytes, respectively). The results of the ROC analysis suggested that plasma α-Syn exhibited better predictive power than erythrocytic α-Syn with a sensitivity of 80.0%, specificity of 97.7%, and a positive predictive value of 77.8%. The expression level of plasma α-Syn correlated well with the age of patients, H-Y stage, MoCA scale, and UPDRS motor scale. On the contrary, there was no correlation between erythrocytic α-Syn level and clinical parameters in this study. Conclusion: Our results suggest that plasma α-Syn could be a specific and sensitive potential diagnostic biomarker for PD.

scholarly journals Regulatory miRNA–mRNA Networks in Parkinson’s Disease

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1410
Author(s):  
Bruno Lopes Santos-Lobato ◽  
Amanda Ferreira Vidal ◽  
Ândrea Ribeiro-dos-Santos
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Target Genes ◽  
Neuronal Survival ◽  
Alpha Synuclein ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
The Brain

Parkinson’s disease (PD) is the second-most common neurodegenerative disease, and its pathophysiology is associated with alpha-synuclein accumulation, oxidative stress, mitochondrial dysfunction, and neuroinflammation. MicroRNAs are small non-coding RNAs that regulate gene expression, and many previous studies have described their dysregulation in plasma, CSF, and in the brain of patients with PD. In this study, we aimed to provide a regulatory network analysis on differentially expressed miRNAs in the brain of patients with PD. Based on our systematic review with a focus on the substantia nigra and the putamen, we found 99 differentially expressed miRNAs in brain samples from patients with PD, which regulate 135 target genes. Five genes associated with neuronal survival (BCL2, CCND1, FOXO3, MYC, and SIRT1) were modulated by dysregulated miRNAs found in the substantia nigra and the putamen of patients with PD. The functional enrichment analysis found FoxO and PI3K-AKT signaling as pathways related to PD. In conclusion, our comprehensive analysis of brain-related miRNA–mRNA regulatory networks in PD showed that mechanisms involving neuronal survival signaling, such as cell cycle control and regulation of autophagy/apoptosis, may be crucial for the neurodegeneration of PD, being a promising way for novel disease-modifying therapies.

scholarly journals Integrated network analysis identifying potential novel drug candidates and targets for Parkinson's disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pusheng Quan ◽  
Kai Wang ◽  
Shi Yan ◽  
Shirong Wen ◽  
Chengqun Wei ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Target ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Control Group ◽  
Drug Candidates ◽  
Novel Drug

AbstractThis study aimed to identify potential novel drug candidates and targets for Parkinson’s disease. First, 970 genes that have been reported to be related to PD were collected from five databases, and functional enrichment analysis of these genes was conducted to investigate their potential mechanisms. Then, we collected drugs and related targets from DrugBank, narrowed the list by proximity scores and Inverted Gene Set Enrichment analysis of drug targets, and identified potential drug candidates for PD treatment. Finally, we compared the expression distribution of the candidate drug-target genes between the PD group and the control group in the public dataset with the largest sample size (GSE99039) in Gene Expression Omnibus. Ten drugs with an FDR < 0.1 and their corresponding targets were identified. Some target genes of the ten drugs significantly overlapped with PD-related genes or already known therapeutic targets for PD. Nine differentially expressed drug-target genes with p < 0.05 were screened. This work will facilitate further research into the possible efficacy of new drugs for PD and will provide valuable clues for drug design.

DNA-methylation analysis of differentially expressed genes in fibroblast cell-lines, derived from monozygotic twins discordant for Parkinson’s disease

2020 ◽  
pp. 73-74
Author(s):  
И.Н. Рыболовлев ◽  
И.Н. Власов ◽  
А.Х. Алиева ◽  
П.А. Сломинский ◽  
М.И. Шадрина
Keyword(s):  
Parkinson’S Disease ◽  
Dna Methylation ◽  
Parkinson's Disease ◽  
Cell Lines ◽  
Differentially Expressed Genes ◽  
Regulation Of Gene Expression ◽  
Monozygotic Twins ◽  
Fibroblast Cell ◽  
Differentially Expressed ◽  
Pathogenesis Related

Болезнь Паркинсона (БП) является многофакторным гетерогенным нейродегенеративным заболеванием. Поскольку этиопатогенез БП недостаточно изучен, кроме поиска и анализа изменений на уровне ДНК, необходимо распространить фокус исследований на другие уровни: транскриптом и метилом. Изменения на уровне эпигенома можно исследовать у лиц с идентичной генетической конституцией, такой «моделью» являются дискордантные по этому заболеванию монозиготные близнецы. В исследовании приняло участие 3 пары фенотипически и генотипически монозиготных близнецов русского происхождения; В исследовании приняло участие 3 пары фенотипически и генотипически монозиготных близнецов русского происхождения. БП была уточнена у одного из каждой пары близнецов; длительность течения болезни у близнеца с БП составило по меньшей мере 7 лет.; длительность течения болезни у близнеца с БП составила по меньшей мере 7 лет. Были проанализированы метиломы крови и отобраны точки варьирующегося метилирования. Нами было найдено 8 дифференциально экспрессирующихся генов, которые могут быть дифференциально метилированы. Были выявлены различия между здоровым близнецом и близнецом с БП по уровню метилирования ДНК для ряда этих генов в клеточных линиях фибробластов. Полученные нами данные могут указывать на участие процесса ДНК-метилирования в регуляции транскрипции кандидатных генов-участников патогенеза БП. In recent years it has been convincingly demonstrated that genetic factors play an important role in progression of Parkinson’s disease (PD). Since the etiology of PD has not been elucidated completely yet, it is crucial to shift focus of the research to the broader areas - to dive into investigations of methylome and transcriptome. Epigenetic regulation of gene expression may take part in pathogenesis of PD. Changes in epigenome can be conveniently investigated in case of individuals with almost identical genetic makeup, and monozygotic twins discordant for PD may be such “model”. 3 pairs phenotypically and genotypically monozygous twins of Russian ancestry were enrolled in the study. PD was diagnosed in one of each pair. The disease duration was at least 7 years. Data on blood methylomes was analyzed. Points of variable methylation in blood methylomes were selected. With this approach, 8 differentially expressed genes were found that also may be differentially methylated. Changes in methylation level for some of this genes were found in monozygotic twins discordant for PD fibroblasts cell-lines between healthy and afflicted siblings. Acquired data might suggest participation of DNA-methylation in transcription regulation of PD pathogenesis-related candidate genes.

Protective effect of hydralazine on a cellular model of Parkinson’s disease: a possible role of hypoxia-inducible factor (HIF)-1α

2020 ◽  
Vol 98 (3) ◽  
pp. 405-414 ◽  
Author(s):  
Mehrnaz Mehrabani ◽  
Mohammad Hadi Nematollahi ◽  
Mojde Esmaeili Tarzi ◽  
Kobra Bahrampour Juybari ◽  
Moslem Abolhassani ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Antioxidant Power ◽  
Expression Levels ◽  
Downstream Target ◽  
Protein Levels ◽  
Ferric Reducing Antioxidant Power ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is a neurodegenerative disease accompanied by a low expression level of cerebral hypoxia-inducible factor (HIF-1α). Hence, activating the hypoxia-signaling pathway may be a favorable therapeutic approach for curing PD. This study explored the efficacy of hydralazine, a well-known antihypertensive agent, for restoring the impaired HIF-1 signaling in PD, with the aid of 6-hydroxydopamine (6-OHDA)-exposed SH-SY5Y cells. The cytotoxicity of hydralazine and 6-OHDA on the SH-SY5Y cells were evaluated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and apoptosis detection assays. The activities of malondialdehyde, nitric oxide (NO), ferric reducing antioxidant power (FRAP), and superoxide dismutase (SOD) were also measured. Expression levels of HIF-1α and its downstream genes at the protein level were assessed by Western blotting. Hydralazine showed no toxic effects on SH-SY5Y cells, at the concentration of ≤50 μmol/L. Hydralazine decreased the levels of apoptosis, malondialdehyde, and NO, and increased the activities of FRAP and SOD in cells exposed to 6-OHDA. Furthermore, hydralazine up-regulated the protein expression levels of HIF-1α, vascular endothelial growth factor, tyrosine hydroxylase, and dopamine transporter in the cells also exposed to 6-OHDA, by comparison with the cells exposed to 6-OHDA alone. In summary, hydralazine priming could attenuate the deleterious effects of 6-OHDA on SH-SY5Y cells by increasing cellular antioxidant capacity, as well as the protein levels of HIF-1α and its downstream target genes.

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