Genome-Scale Expression Pattern of Long Non-Coding RNAs in Chinese Uyghur Patients with Parkinson’s Disease

Parkinson’s disease (PD) has been shown to affect approximately 1% of the persons aged more than 65 years. This multifactorial disorder has been associated with abnormal function of NF-κB signals. In this research, we have evaluated expressions of NF-κB-related long non-coding RNAs in the circulation of PD patients compared with healthy controls. Expression of PACER was lower in total PD patients compared with healthy persons (Ratio of mean expressions (RME)=0.32, P value<0.001). This pattern was also evident among males (RME=0.25, P value<0.001). Expression of DILC was higher in total PD patients (RME=4.07, P value<0.001), and in both sex-based subgroups (RME=3.77, P value=0.01 and RME=4.25, P value<0.001, for females and males, respectively). Similarly, CEBPA was significantly over-expressed in total PD patients (RME=14.76, P value<0.001), and in both sex-based subgroups (RME=12.42, P value<0.001 and RME=15.80, P value<0.001, for females and males, respectively). ATG5 had a similar expression pattern (RME=2.6, P value=1E-08, RME=1.73, P value=0.03 and RME=3.09, P value=1E-07, for total cases, females and males, respectively). H19 was up-regulated in total cases and male cases compared with corresponding controls (RME=2.19, P value<0.001, RME=2.68, P value=0.01, respectively). Finally, HNFA1-AS was down-regulated in all comparisons (RME=0.10, P value=2E-06, RME=0.08, P value<0.001 and RME=0.12, P value<0.001, for total cases, females and males, respectively). Among PD patients, expressions of NKILA and ADINR were robustly correlated with each other (r=0.75, P value=2.40E-10). In addition, expression levels of DICER1-AS were significantly correlated with those of ADINR, PACER and H19 in these patients (r=0.73, P value=1.76E-9; r=0.72, P value=5.15E-09 and r=0.72, P value=3.09E-09, respectively). Correlation analyses among healthy controls revealed robust correlations between CHAST and CEBPA (r=0.84, P value=3.09E-09), NKILA and ADINR (r=0.80, P value=4.24E-12) as well as between DILC and CHAST (r=0.76, P value=1.70E-10). CEBPA had the best parameters among all assessed genes (AUC=0.96, Sensitivity=0.90 and specificity=0.97). DILC and ATG5 were the most appropriate markers after CEBPA with AUC values of 0.82 and 0.80, respectively. Most notably, combination of all genes improved AUC, sensitivity and specificity parameters to 1, 0.97 and 0.99, respectively. Cumulatively, the current study provides evidence for participation of NF-κB-related lncRNAs in the pathoetiology of PD.

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Assessment of the role of non-coding RNAs in the pathophysiology of Parkinson's disease

European Journal of Pharmacology ◽

10.1016/j.ejphar.2021.173914 ◽

2021 ◽

Vol 896 ◽

pp. 173914

Author(s):

Omidvar Rezaei ◽

Saeedeh Nateghinia ◽

Mehrdad A. Estiar ◽

Mohammad Taheri ◽

Soudeh Ghafouri-Fard

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Non Coding Rnas

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Chemical and Biological Molecules Involved in Differentiation, Maturation, and Survival of Dopaminergic Neurons in Health and Parkinson’s Disease: Physiological Aspects and Clinical Implications

Biomedicines ◽

10.3390/biomedicines9070754 ◽

2021 ◽

Vol 9 (7) ◽

pp. 754

Author(s):

Giulia Gaggi ◽

Andrea Di Credico ◽

Pascal Izzicupo ◽

Giovanni Iannetti ◽

Angela Di Baldassarre ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Potential Role ◽

High Efficiency ◽

Biological Molecules ◽

Alternative Approach ◽

Non Coding Rnas ◽

Set Up

Parkinson’s disease (PD) is one of the most common neurodegenerative disease characterized by a specific and progressive loss of dopaminergic (DA) neurons and dopamine, causing motor dysfunctions and impaired movements. Unfortunately, available therapies can partially treat the motor symptoms, but they have no effect on non-motor features. In addition, the therapeutic effect reduces gradually, and the prolonged use of drugs leads to a significative increase in the number of adverse events. For these reasons, an alternative approach that allows the replacement or the improved survival of DA neurons is very appealing for the treatment of PD patients and recently the first human clinical trials for DA neurons replacement have been set up. Here, we review the role of chemical and biological molecules that are involved in the development, survival and differentiation of DA neurons. In particular, we review the chemical small molecules used to differentiate different type of stem cells into DA neurons with high efficiency; the role of microRNAs and long non-coding RNAs both in DA neurons development/survival as far as in the pathogenesis of PD; and, finally, we dissect the potential role of exosomes carrying biological molecules as treatment of PD.

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Systematic Investigation of Mouse Models of Parkinson’s Disease by Transcriptome Mapping on a Brain-Specific Genome-Scale Metabolic Network

Molecular Omics ◽

10.1039/d0mo00135j ◽

2021 ◽

Author(s):

Ecehan Abdik ◽

Tunahan Cakir

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Metabolic Network ◽

Mouse Models ◽

Mus Musculus ◽

Metabolic Networks ◽

Systematic Investigation ◽

Omics Data ◽

Metabolic Alterations ◽

Genome Scale

Genome-scale metabolic networks enable systemic investigation of metabolic alterations caused by diseases by providing interpretation of omics data. Although Mus musculus (mouse) is one of the most commonly used model...

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Genome-scale methylation analysis of Parkinson's disease patients' brains reveals DNA hypomethylation and increased mRNA expression of cytochrome P450 2E1

Neurogenetics ◽

10.1007/s10048-011-0308-3 ◽

2012 ◽

Vol 13 (1) ◽

pp. 87-91 ◽

Cited By ~ 60

Author(s):

Oliver Kaut ◽

Ina Schmitt ◽

Ullrich Wüllner

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cytochrome P450 ◽

Mrna Expression ◽

Cytochrome P450 2E1 ◽

Dna Hypomethylation ◽

Methylation Analysis ◽

Genome Scale

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Non-Coding RNAs in the Brain-Heart Axis: The Case of Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21186513 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6513 ◽

Cited By ~ 1

Author(s):

Shubhra Acharya ◽

Antonio Salgado-Somoza ◽

Francesca Maria Stefanizzi ◽

Andrew I. Lumley ◽

Lu Zhang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

High Throughput ◽

Regulatory Networks ◽

Current Knowledge ◽

Circular Rnas ◽

Clinical Markers ◽

Wide Range ◽

Non Coding Rnas ◽

The Brain

Parkinson’s disease (PD) is a complex and heterogeneous disorder involving multiple genetic and environmental influences. Although a wide range of PD risk factors and clinical markers for the symptomatic motor stage of the disease have been identified, there are still no reliable biomarkers available for the early pre-motor phase of PD and for predicting disease progression. High-throughput RNA-based biomarker profiling and modeling may provide a means to exploit the joint information content from a multitude of markers to derive diagnostic and prognostic signatures. In the field of PD biomarker research, currently, no clinically validated RNA-based biomarker models are available, but previous studies reported several significantly disease-associated changes in RNA abundances and activities in multiple human tissues and body fluids. Here, we review the current knowledge of the regulation and function of non-coding RNAs in PD, focusing on microRNAs, long non-coding RNAs, and circular RNAs. Since there is growing evidence for functional interactions between the heart and the brain, we discuss the benefits of studying the role of non-coding RNAs in organ interactions when deciphering the complex regulatory networks involved in PD progression. We finally review important concepts of harmonization and curation of high throughput datasets, and we discuss the potential of systems biomedicine to derive and evaluate RNA biomarker signatures from high-throughput expression data.

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Altered protein expression pattern in skin fibroblasts from parkin -mutant early-onset Parkinson's disease patients

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ◽

10.1016/j.bbadis.2015.06.015 ◽

2015 ◽

Vol 1852 (9) ◽

pp. 1960-1970 ◽

Cited By ~ 15

Author(s):

Rosa Lippolis ◽

Rosa Anna Siciliano ◽

Consiglia Pacelli ◽

Anna Ferretta ◽

Maria Fiorella Mazzeo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Protein Expression ◽

Expression Pattern ◽

Early Onset ◽

Skin Fibroblasts ◽

Protein Expression Pattern ◽

Altered Protein ◽

Early Onset Parkinson’S Disease

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Circulating Inflammatory miRNAs Associated with Parkinson’s Disease Pathophysiology

Biomolecules ◽

10.3390/biom10060945 ◽

2020 ◽

Vol 10 (6) ◽

pp. 945 ◽

Cited By ~ 1

Author(s):

Sara R. Oliveira ◽

Pedro A. Dionísio ◽

Leonor Correia Guedes ◽

Nilza Gonçalves ◽

Miguel Coelho ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Roc Curve ◽

Operating Characteristic ◽

Disease Diagnosis ◽

Healthy Controls ◽

Roc Curve Analysis ◽

Additional Group ◽

Lrrk2 Gene ◽

Non Coding Rnas

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 (LRRK2) 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.

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