Bone-Derived Factors as Potential Biomarkers for Parkinson’s Disease
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ABSTRACT:
SUBMITTER: Lin Y
PROVIDER: S-EPMC7959739 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
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Project description:The identification of biomarkers for early diagnosis of Parkinson's disease (PD) prior to the onset of symptoms may improve the effectiveness of therapy. To identify potential biomarkers, we downloaded microarray datasets of PD from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between PD and normal control (NC) groups were obtained, and the feature selection procedure and classification model were used to identify optimal diagnostic gene biomarkers for PD. A total of 1229 genes (640 up-regulated and 589 down-regulated) were obtained for PD, and nine DEGs (PTGDS, GPX3, SLC25A20, CACNA1D, LRRN3, POLR1D, ARHGAP26, TNFSF14 and VPS11) were selected as optimal PD biomarkers with great diagnostic value. These nine DEGs were significantly enriched in regulation of circadian sleep/wake cycle, sleep and gonadotropin-releasing hormone signaling pathway. Finally, we examined the expression of GPX3, SLC25A20, LRRN3 and POLR1D in blood samples of patients with PD by qRT-PCR. GPX3, LRRN3 and POLR1D exhibited the same expression pattern as in our analysis. In conclusion, this study identified nine DEGs that may serve as potential biomarkers of PD.
| S-EPMC6668373 | biostudies-literature
Project description:PurposeThe purpose of this study was to identify the potential exosome-derived microRNAs (miRNAs) related to prostate cancer (Pca) bone metastasis.MethodsTwo datasets were collected. One dataset was from the authors' institute, for which two groups of 10 patients each were designed: in the first one, the patients had early-stage localised Pca without bone metastasis, and in the other, the patients presented with Pca with bone metastasis. Then, the miRNA expression profiles of the blood exosomes were obtained and analysed. The other dataset was a public dataset of the miRNA expression transcriptome (GSE26964), which was downloaded from Gene Expression Omnibus (GEO). The results of both datasets were jointly analysed and the most bone-metastatic-related differentially expressed miRNAs (diff-miRNAs) were identified and further validated. Finally, a series of bioinformatics analyses were performed and the relationship between target genes of the diff-miRNAs and the pathogenesis and progression of bone metastasis of Pca were studied.ResultsFrom the authors' dataset, in all, 313 diff-miRNAs were identified, of which 205 were up-regulated while 108 were down-regulated. From the GSE26964 dataset, 107 diff-miRNAs were found, of which 44 were up-regulated and 63 were down-regulated. Taking the intersection of the results of both datasets, four diff-miRNAs were identified: hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613. In all, 94 target genes of the four diff-miRNAs were predicted. After considering the intersection of the results from the GSE32269 dataset, we obtained 25 target genes. Although either positive or negative correlations were found among the diff-miRNAs with some of the target genes, there is a lack of evidence on how such correlations regulate the development and promotion of Pca bone metastasis.ConclusionHsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613 are potential biomarkers for Pca bone metastasis.
| S-EPMC9167626 | biostudies-literature
Project description:BackgroundManagement of motor complications (MC) represents a major challenge in the long-term treatment of Parkinson's disease (PD) patients. In this context, the role of peripheral adaptive immunity may provide new insights, since neuroinflammatory mechanisms have been proved crucial in the disease.ObjectiveThe aim of this study was to analyze the transcription factors genes involved in CD4 + T cells development to uncover specific molecular signatures in patients with (PMC) and without (WMC) motor complications.MethodsmRNA levels of CD4 + T lymphocytes transcription factor genes TBX21, STAT1, STAT3, STAT4, STAT6, RORC, GATA3, FOXP3, and NR4A2 were measured from 40 PD patients, divided into two groups according to motor complications. Also, 40 age- and sex-matched healthy controls were enrolled.ResultsWMC patients had higher levels of STAT1 and NR4A2 (p = 0.004; p = 0.003), whereas in PMC we found higher levels of STAT6 (p = 0.04). Also, a ROC curve analysis confirmed STAT1 and NR4A2 as feasible biomarkers to discriminate WMC (AUC = 0.76, 95%CI 0.59-0.92, p = 0.005; AUC = 0.75, 95%CI 0.58-0.90, p = 0.007). Similarly, STAT6 detected PMC patients (AUC = 0.69, 95%CI 0.52-0.86, p = 0.037).ConclusionThese results provide evidence of different molecular signatures in CD 4 + T cells of PD patients with and without MC, thus suggesting their potential as biomarkers of MC development.
| S-EPMC8150526 | biostudies-literature
Project description:Parkinson's disease (PD) is a widespread neurodegenerative disorder. Despite the intensive studies of this pathology, in general, the picture of the etiopathogenesis has still not been clarified fully. To understand better the mechanisms underlying the pathogenesis of PD, we analyzed the expression of 10 genes in the peripheral blood of treated and untreated patients with PD. 35 untreated patients with PD and 12 treated patients with Parkinson's disease (Hoehn and Yahr scores 1-2) were studied. An analysis of the mRNA levels of ATP13A2, PARK2, PARK7, PINK1, LRRK2, SNCA, ALDH1A1, PDHB, PPARGC1A, and ZNF746 genes in the peripheral blood of patients was carried out using reverse transcription followed by real-time PCR. A statistically significant and specific increase by more than 1.5-fold in the expression of the ATP13A2, PARK7, and ZNF746 genes was observed in patients with PD. Based on these results, it can be suggested that the upregulation of the mRNA levels of ATP13A2, PARK7, and ZNF746 in untreated patients in the earliest clinical stages can also be observed in the preclinical stages of PD, and that these genes can be considered as potential biomarkers of the preclinical stage of PD.
| S-EPMC4592918 | biostudies-literature
Project description:BackgroundBlood-based test for predicting disease progression and early diagnosis of Parkinson's disease (PD) is an unmet need in the clinic. The profiles of microRNAs (miRNAs) are regarded as potential diagnostic biomarkers for human diseases, whereas miRNAs in the periphery are susceptible to the influence of various components. MiRNAs enriched in serum extracellular vesicles (EVs) have demonstrated disease-specific advantages in diagnosis due to their high abundance, stability and resistance to degradation. This study was aimed to screen differentially expressed EV-derived miRNAs between healthy controls and PD patients to aid in diagnosis of PD.MethodsA total of 31 healthy controls and 72 patients with a diagnosis of PD at different Hoehn and Yahr stages in Tangdu Hospital were included. In total, 185 differentially expressed miRNAs were obtained through RNA sequencing of serum EVs as well as edgeR and t-test analyses. Subsequently, the weighted gene co-expression network analysis (WGCNA) was utilized to identify the commonly expressed miRNAs in all stages of PD by constructing connections between modules, and specifically expressed miRNAs in each stage of PD by functional enrichment analysis. After aligning these miRNAs with PD-related miRNAs in Human miRNA Disease Database, the screened miRNAs were further validated by receiver operating characteristic (ROC) curves and quantitative real-time polymerase chain reaction (qRT-PCR) using peripheral blood EVs from 40 more participants.ResultsWGCNA showed that 4 miRNAs were commonly associated with all stages of PD and 13 miRNAs were specifically associated with different stages of PD. Of the 17 obtained miRNAs, 7 were validated by ROC curve analysis and 7 were verified in 40 more participants by qRT-PCR. Six miRNAs were verified by both methods, which included 2 miRNAs that were commonly expressed in all stages of PD and 4 miRNAs that were specifically expressed in different stages of PD.ConclusionsThe 6 serum EV-derived miRNAs, hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-199a-3p, hsa-miR-28-5p, hsa-miR-22-5p and hsa-miR-151a-5p, may potentially be used as biomarkers for PD progression and for early diagnosis of PD in populations.
| S-EPMC8317324 | biostudies-literature
Project description:Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset.
| S-EPMC5619098 | biostudies-literature
Project description:Patients with Parkinson's disease (PD) oftentimes develop olfactory dysfunction in their early stages, converting the nasal environment into a useful source of potential biomarkers. Here we determined the possible application of nasal fluid cells for PD biomarker identification. Thirty PD patients and 13 age-matched healthy controls were enrolled in this study. Messenger RNA levels of selected PD-related genes were monitored through real-time quantitative PCR. Target gene transcripts can be efficiently amplified from the cDNA library from human nasal fluid cell pellets. And subsequent analysis showed both a marked downregulation of parkin transcripts and an upregulation of AIMP2 in PD patients when compared to controls (cutoff value = 1.753 for with 84.2% sensitivity and 84.6% specificity; 0.359 for parkin with 76.7% sensitivity and 76.9 specificity). Moreover, alteration pattern of parkin and AIMP2 in PD was distinct from another neurodegenerative disease, multiple system atrophy. Analysis in both the early and late stages of PD cases reported that parkin levels inversely correlated with PD stages. Our results validate the practical value of easily accessible nasal fluid cells and the utility of both AIMP2 and parkin as potential biomarkers for PD diagnosis.
| S-EPMC6668404 | biostudies-literature
Project description:Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. The purpose of this study was to analyze the profile of the tear proteome of patients with idiopathic PD (iPD), carriers of the E46K-SNCA mutation and healthy subjects (CT) and to identify biomarkers for the early diagnosis of PD. An observational, prospective and case-control pilot study was carried out in 24 patients with iPD, 3 carriers of the E46K-SNCA mutation and 27 CT subjects. The patients' neurological involvement was scored and their tear samples were analyzed using nano-liquid chromatography-mass spectrometry (nLC-MS/MS). These analyses led to the identification of 560 tear proteins in which some of the deregulated proteins were involved in immune response, apoptosis, collagen degradation, protein synthesis, defense and altered lysosomal function. Of these proteins, six related to neurodegenerative processes, showed a good capacity to classify patients and controls. These findings revealed that some proteins were upregulated in the tears of PD patients, mainly those involved in lysosomal function. It is worth highlighting the importance of this study in identifying tear proteins implicated in neurodegeneration and its relationship with PD patients with an aggressive disease phenotype.
2022-02-14 | PXD028811 | Pride
Project description:BackgroundNeuroinflammation plays a key role in PD pathogenesis, and allogeneic bone marrow-derived mesenchymal stem cells can be used as an immunomodulatory therapy.ObjectiveThe objective of this study was to prove the safety and tolerability of intravenous allogeneic bone marrow-derived mesenchymal stem cells in PD patients.MethodsThis was a 12-month single-center open-label dose-escalation phase 1 study of 20 subjects with mild/moderate PD assigned to a single intravenous infusion of 1 of 4 doses: 1, 3, 6, or 10 × 106 allogeneic bone marrow-derived mesenchymal stem cells/kg, evaluated 3, 12, 24, and 52 weeks postinfusion. Primary outcome safety measures included transfusion reaction, study-related adverse events, and immunogenic responses. Secondary outcomes included impact on peripheral markers, PD progression, and changes in brain perfusion.ResultsThere were no serious adverse reactions related to the infusion and no responses to donor-specific human leukocyte antigens. Most common treatment-emergent adverse events were dyskinesias (20%, n = 4) with 1 emergent and 3 exacerbations; and hypertension (20%, n = 4) with 3 transient episodes and 1 requiring medical intervention. One possibly related serious adverse event occurred in a patient with a 4-year history of lymphocytosis who developed asymptomatic chronic lymphocytic leukemia. Peripheral inflammation markers appear to be reduced at 52 weeks in the highest dose including, tumor necrosis factor-α (P < 0.05), chemokine (C-C motif) ligand 22 (P < 0.05), whereas brain-derived neurotrophic factor (P < 0.05) increased. The highest dose seems to have demonstrated the most significant effect at 52 weeks, reducing the OFF state UPDRS motor, -14.4 (P < 0.01), and total, -20.8 (P < 0.05), scores.ConclusionA single intravenous infusion of allogeneic bone marrow-derived mesenchymal stem cells at doses of 1, 3, 6, or 10 × 106 allogeneic bone marrow-derived mesenchymal stem cells/kg is safe, well tolerated, and not immunogenic in mild/moderate PD patients. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
| S-EPMC8451899 | biostudies-literature
Project description:OBJECTIVE:To identify Parkinson's disease (PD)-associated deregulated pathways and genes, to further elucidate the pathogenesis of PD. METHODS:Dataset GSE100054 was downloaded from the Gene Expression Omnibus, and differentially expressed genes (DEGs) in PD samples were identified. Functional enrichment analyses were conducted for the DEGs. The top 10 hub genes in the protein-protein interaction (PPI) network were screened out and used to construct a support vector machine (SVM) model. The expression of the top 10 genes was then validated in another dataset, GSE46129, and a clinical patient cohort. RESULTS:A total of 333 DEGs were identified. The DEGs were clustered into two gene sets that were significantly enriched in 12 pathways, of which 8 were significantly deregulated in PD, including cytokine-cytokine receptor interaction, gap junction, and actin cytoskeleton regulation. The signature of the top 10 hub genes in the PPI network was used to construct the SVM model, which had high performance for predicting PD. Of the 10 genes, GP1BA, GP6, ITGB5, and P2RY12 were independent risk factors of PD. CONCLUSION:Genes such as GP1BA, GP6, P2RY12, and ITGB5 play critical roles in PD pathology through pathways including cytokine-cytokine receptor interaction, gap junctions, and actin cytoskeleton regulation.
| S-EPMC7543192 | biostudies-literature