<scp>MicroRNA</scp> Deregulation in Blood Serum Identifies Multiple System Atrophy Altered Pathways

Pérez‐Soriano, Alexandra; Bravo, Paloma; Soto, M. Álvarez-Mon; Infante, Jon; Fernández, Manel; Valldeoriola, Francesc; Muñoz, Esteban; Compta, Yaroslau; Tolosa, Eduard; Garrido, Alícia; Ezquerra, Mario; Fernández‐Santiago, Rubén; Martí, María‐José

doi:10.1002/mds.28143

Cited by 15 publications

(16 citation statements)

References 37 publications

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“…We found salivary miR-29a-3p has adequate specificity for differentiating idiopathic PD from MSA and ET. Previous studies indicated that serum miRNA-7641 and miRNA-191 could differentiate MSA from PD, and that plasma miR-4639-5p had adequate sensitivity and specificity to discriminate between PD and ET patients (8,9). Despite these recognized limitations of diagnostic accuracy, salivary miRNA has promising diagnostic value.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

“…However, only a few studies have evaluated the disease specificity of miRNAs among PD, MSA and ET. Serum miR-7641, miR-191 and plasma miR-19b-3p may be useful for differentiating PD and multiple system atrophy (MSA) (7,8). Plasma hsa-miR-4639-5p may discriminate between PD patients and ET patients (9).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…We used two endogenous and one exogenous miRNA simultaneously for normalization in all RT‐qPCR comparisons 17,18 . As endogenous normalizers, we selected hsa‐miR‐320a‐3p and hsa‐miR‐6727‐5p among the most stable miRNAs from the array across all samples as identified using the NormFinder software 19 in other α‐synucleinopathies studies in our population, i.e., MSA 20 and LRRK2‐associated PD (Marta Soto, Manel Fernández, Paloma Bravo, Alicia Garrido, Antonio Sánchez‐Rodríguez, María Rivera‐Sánchez, María Sierra, Paula Melón, Anna Naito, Bradford Casey, Eduardo Tolosa, María‐José Martí, Jon Infante, Mario Ezquerra and Rubén Fernández‐Santiago). As an exogenous normalizer, we used the Caenorhabditis elegans miRNA cel‐miR‐39‐3p added to all serum samples at a final concentration of 5 pM 18 .…”

Section: Methodsmentioning

confidence: 99%

Serum MicroRNAs Predict Isolated Rapid Eye Movement Sleep Behavior Disorder and Lewy Body Diseases

et al. 2022

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Background Isolated rapid eye movement sleep behavior disorder (IRBD) is a well‐established clinical risk factor for Lewy body diseases (LBDs), such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Objective To elucidate whether serum microRNA (miRNA) deregulation in IRBD can antedate the diagnosis of LBD by performing a longitudinal study in different progression stages of IRBD before and after LBD diagnosis and assessing the predictive performance of differentially expressed miRNAs by machine learning–based modeling. Methods Using genome‐wide miRNA analysis and real‐time quantitative polymerase chain reaction validation, we assessed serum miRNA profiles from patients with IRBD stratified by dopamine transporter (DaT) single‐photon emission computed tomography into DaT‐negative IRBD (n = 17) and DaT‐positive IRBD (n = 21), IRBD phenoconverted into LBD (n = 13), and controls (n = 20). Longitudinally, we followed up the IRBD cohort by studying three time point serum samples over 26 months. Results We found sustained cross‐sectional and longitudinal deregulation of 12 miRNAs across the RBD continuum, including DaT‐negative IRBD, DaT‐positive IRBD, and LBD phenoconverted IRBD (let‐7c‐5p, miR‐19b‐3p, miR‐140, miR‐22‐3p, miR‐221‐3p, miR‐24‐3p, miR‐25‐3p, miR‐29c‐3p, miR‐361‐5p, miR‐425‐5p, miR‐4505, and miR‐451a) (false discovery rate P < 0.05). Age‐ and sex‐adjusted predictive modeling based on the 12 differentially expressed miRNA biosignatures discriminated IRBD and PD or DLB from controls with an area under the curve of 98% (95% confidence interval: 89–99%). Conclusions Besides clinical diagnosis of IRBD or imaging markers such as DaT single‐photon emission computed tomography, specific miRNA biosignatures alone hold promise as progression biomarkers for patients with IRBD for predicting PD and DLB clinical outcomes. Further miRNA studies in other PD at‐risk populations, such as LRRK2 mutation asymptomatic carriers or hyposmic subjects, are warranted. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

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“…The synthesis of ferritin heavy chains is dependent on the release of free iron and cytoplasmic iron efflux when the membrane transport protein Fe-ATPase is activated, leading to a decrease in intracellular free Fe 2+ content and preventing the occurrence of Fentonian iron death-induced cell damage (Götz et al, 2004). Mitochondrial RNA (mtRNA) may alter iron death by regulating the expression of Nrf2 (Pérez-Soriano et al, 2020), where different isoforms have different regulation of Nrf2, inducing activation of Nrf2 pathway through inhibition of Keap1 or increasing the aggregation of Nrf2 in the nucleus through Cullin-3 (Cul3). Heme oxygenase (HO) is a protective factor, metabolite with Fe2+ production, and its Nrf2/HO-1 pathway can regulate intracellular iron concentration (LIP).…”

Section: Nrf2 and Iron Deathmentioning

confidence: 99%

Role of Nrf2 in Parkinson’s Disease: Toward New Perspectives

Yang

Yang²,

Zhang³

2022

Front. Pharmacol.

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Parkinson’s disease (PD) is one of the most common and chronic degenerative diseases in the central nervous system. The main pathology of PD formation is the progressive loss of dopaminergic neurons in substantia nigra and the formation of α-synuclein-rich Lewy bodies. The pathogenesis of PD is not caused by any single independent factor. The diversity of these independent factors of PD, such as iron accumulation, oxidative stress, neuroinflammation, mitochondrial dysfunction, age, environment, and heredity, makes the research progress of PD slow. Nrf2 has been well-known to be closely associated with the pathogenesis of PD and could regulate these induced factors development. Nrf2 activation could protect dopaminergic neurons and slow down the progression of PD. This review summarized the role of Nrf2 pathway on the pathogenesis of PD. Regulation of Nrf2 pathway might be one of the promising strategies to prevent and treat PD.

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MicroRNA Deregulation in Blood Serum Identifies Multiple System Atrophy Altered Pathways

Cited by 15 publications

References 37 publications

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

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

Serum MicroRNAs Predict Isolated Rapid Eye Movement Sleep Behavior Disorder and Lewy Body Diseases

Role of Nrf2 in Parkinson’s Disease: Toward New Perspectives

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