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

Rezaei, Omidvar; Nateghinia, Saeedeh; Estiar, Mehrdad Asghari; Taheri, Mohammad; Ghafouri‐Fard, Soudeh

doi:10.1016/j.ejphar.2021.173914

Cited by 27 publications

(14 citation statements)

References 64 publications

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“…A former study showed that hsa-miR-7, which was downregulated in the substantia nigra according to our review, is a direct regulator of SNCA, reducing its expression in a cell model and in an MPTP PD murine model [34]. Considering the miRNAs associated with both substantia nigra and putamen, we found that hsa-miR-34b and hsa-miR-95-hsa-miR-34b are associated with a reduction in the expression of alpha-synuclein [35], DJ-1, and Parkin [6], while hsa-miR-95 regulates the lysosomal function through the enzyme sulfatase-modifying factor 1 [36], and it was downregulated in pregnant women with multiple sclerosis [37]. To compare with another prevalent neurodegenerative disease, miRNAs such as hsa-miR-132 and hsa-miR-339-5p could be found in the brain of both PD and Alzheimer's disease patients [38].…”

Section: Discussionmentioning

confidence: 64%

“…Cells 2021, 10, 1410 2 of 16 For instance, it was demonstrated that hsa-miR-34b and hsa-miR-34c are downregulated in PD, reducing the levels of DJ-1 and Parkin in the brain, two proteins involved in the ubiquitin-proteasome system in neurons, causing cell death. Furthermore, hsa-miR-4639-5p is upregulated in PD and inhibits DJ-1, also promoting cell death [6]. The dysregulation of these miRNAs shows how these molecules can modulate the pathophysiology of PD.…”

Section: Introductionmentioning

confidence: 99%

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Regulatory miRNA–mRNA Networks in Parkinson’s Disease

Santos‐Lobato

Vidal

Ribeiro-dos-Santos

2021

Cells

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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.

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Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Regulatory miRNA–mRNA Networks in Parkinson’s Disease

Santos‐Lobato

Vidal

Ribeiro-dos-Santos

2021

Cells

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“…Only recently has it been discovered that the roles of RNAs are not limited to bridging genes and proteins (Carvalho Barbosa et al, 2020 ). The last decade has witnessed the discovery and annotation of thousands of both housekeeping and regulatory ncRNAs, which are emerging as key regulators of gene expression at the transcriptional or post-transcriptional level (Li et al, 2015 ; Merry et al, 2015 ; Yildirim et al, 2020 ; Rezaei et al, 2021 ). Several subtypes of regulatory ncRNAs, including miRNAs, lncRNAs, and circRNAs, are involved in the pathogenesis of PD (Majidinia et al, 2016 ).…”

Section: How Do the Ncrnas Regulate Parkinson’s Disease?mentioning

confidence: 99%

Crosstalk between regulatory non-coding RNAs and oxidative stress in Parkinson’s disease

Zhang

Liu

et al. 2022

Front. Aging Neurosci.

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Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease, which imposes an ever-increasing burden on society. Many studies have indicated that oxidative stress may play an important role in Parkinson’s disease through multiple processes related to dysfunction or loss of neurons. Besides, several subtypes of non-coding RNAs are found to be involved in this neurodegenerative disorder. However, the interplay between oxidative stress and regulatory non-coding RNAs in Parkinson’s disease remains to be clarified. In this article, we comprehensively survey and overview the role of regulatory ncRNAs in combination with oxidative stress in Parkinson’s disease. The interaction between them is also summarized. We aim to provide readers with a relatively novel insight into the pathogenesis of Parkinson’s disease, which would contribute to the development of pre-clinical diagnosis and treatment.

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“…Cumulatively, dopamine-associated oxidative stress, dysfunction of synaptic vesicles and misfolding of α-synuclein produce an extending vicious cycle which perpetually results in death of dopaminergic neurons ( 3 ). PD has been associated with dysregulation of several transcripts among them are long non-coding RNAs (lncRNAs) ( 4 ). LncRNAs have possible role in brain development.…”

Section: Introductionmentioning

confidence: 99%

Parkinson’s Disease Is Associated With Dysregulation of Circulatory Levels of lncRNAs

et al. 2021

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Long non-coding RNAs (lncRNAs) have been recently reported to be involved in the pathoetiology of Parkinson’s disease (PD). Circulatory levels of lncRNAs might be used as markers for PD. In the present work, we measured expression levels of HULC, PVT1, MEG3, SPRY4-IT1, LINC-ROR and DSCAM-AS1 lncRNAs in the circulation of patients with PD versus healthy controls. Expression of HULC was lower in total patients compared with total controls (Expression ratio (ER)=0.19, adjusted P value<0.0001) as well as in female patients compared with female controls (ER=0.071, adjusted P value=0.0004). Expression of PVT1 was lower in total patients compared with total controls (ER=0.55, adjusted P value=0.0124). Expression of DSCAM-AS1 was higher in total patients compared with total controls (ER=5.67, P value=0.0029) and in male patients compared with male controls (ER=9.526, adjusted P value=0.0024). Expression of SPRY4-IT was higher in total patients compared with total controls (ER=2.64, adjusted P value<0.02) and in male patients compared with male controls (ER=3.43, P value<0.03). Expression of LINC-ROR was higher in total patients compared with total controls (ER=10.36, adjusted P value<0.0001) and in both male and female patients compared with sex-matched controls (ER=4.57, adjusted P value=0.03 and ER=23.47, adjusted P value=0.0019, respectively). Finally, expression of MEG3 was higher in total patients compared with total controls (ER=13.94, adjusted P value<0.0001) and in both male and female patients compared with sex-matched controls (ER=8.60, adjusted P value<0.004 and ER=22.58, adjusted P value<0.0085, respectively). ROC curve analysis revealed that MEG3 and LINC-ROR have diagnostic power of 0.77 and 0.73, respectively. Other lncRNAs had AUC values less than 0.7. Expression of none of lncRNAs was correlated with age of patients, disease duration, disease stage, MMSE or UPDRS. The current study provides further evidence for dysregulation of lncRNAs in the circulation of PD patients.

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

Cited by 27 publications

References 64 publications

Regulatory miRNA–mRNA Networks in Parkinson’s Disease

Regulatory miRNA–mRNA Networks in Parkinson’s Disease

Crosstalk between regulatory non-coding RNAs and oxidative stress in Parkinson’s disease

Parkinson’s Disease Is Associated With Dysregulation of Circulatory Levels of lncRNAs

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