microRNAs involved in Parkinson's disease: A systematic review

Silva, Franciele Cascaes da; Iop, Rodrigo da Rosa; Vietta, Giovanna Grünewald; Kair, Diego Alessandro; Filho, Paulo José Barbosa Gutierres; Alvarenga, José Gustavo Souza de; Silva, Rudney da

doi:10.3892/mmr.2016.5759

Cited by 35 publications

(18 citation statements)

References 56 publications

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“…Along these lines, qualitative reviews on the role of miRNAs in PD are largely based on a (subjective) selection of the literature that does not hold up to systematic meta‐analyses. For instance, in five recent articles reviewing the role of miRNAs in PD based on human expression or on experimental data (including one systematic review), 190 miRNAs were highlighted as being potentially relevant in PD (Supplementary Table 8). Of these, expression data were lacking or sparse for 113 (59%), that is, they could not be meta‐analyzed here.…”

Section: Discussionmentioning

confidence: 99%

Meta‐analyses identify differentially expressed microRNAs in Parkinson's disease

Schulz

Takousis

Wohlers

et al. 2019

Annals of Neurology

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Objective: MicroRNA (miRNA)-mediated (dys)regulation of gene expression has been implicated in Parkinson's disease (PD), although results of miRNA expression studies remain inconclusive. We aimed to identify miRNAs that show consistent differential expression across all published expression studies in PD. Methods: We performed a systematic literature search on miRNA 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 miRNAs assessed in three or more independent data sets. Meta-analyses were performed using effect-size-and p-value-based methods, as applicable. Results: After screening 599 publications, we identified 47 data sets eligible for meta-analysis. On these, we performed 160 meta-analyses on miRNAs quantified in brain (n = 125), blood (n = 31), or CSF (n = 4). Twenty-one meta-analyses were performed using effect sizes. We identified 13 significantly (Bonferroni-adjusted α = 3.13 × 10 -4 ) differentially expressed miRNAs 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 genome-wide association study data for target genes of brain miRNAs showed significant association (α = 9.40 × 10 -5 ) of genetic variants in nine loci. Interpretation: We identified several miRNAs 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 miRNAs as biomarkers for diagnosis, progression, or prediction of PD. ANN NEUROL 2019;85:835-851 P arkinson's disease (PD) is the second-most common neurodegenerative disease affecting 1% of people over the age of 60. The increasing incidence of PD in industrialized, aging populations constitutes a growing socioeconomic burden. 1 Idiopathic PD results from a combination of multiple genetic 2-4 and environmental/lifestyle factors. 5,6 However, the currently known risk factors only explain a small fraction of the phenotypic variance of PD. Likewise, PD View this article online at wileyonlinelibrary.com.

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Section: Discussionmentioning

confidence: 99%

Meta‐analyses identify differentially expressed microRNAs in Parkinson's disease

Schulz

Takousis

Wohlers

et al. 2019

Annals of Neurology

View full text Add to dashboard Cite

show abstract

“…Along these lines, qualitative reviews on the role of miRNAs in PD are largely based on a (subjective) selection of the literature that does not hold up to systematic meta-analyses. For instance, in five recent articles reviewing the role of miRNAs in PD based on human expression or on experimental data (7,24-27) (including one systematic review (27)), 190 miRNAs were highlighted as being potentially relevant in PD (Supplementary 8). Of these, expression data were lacking or sparse for 113 (59%), i.e.…”

Section: Discussionmentioning

confidence: 99%

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

Takousis

Wohlers

Itua

et al. 2018

Preprint

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ObjectiveMicroRNA-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.

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“…In murine embryonic brain cortices during hypoxia-induced neuronal apoptosis, the miR-23b-27b cluster was also found to be downregulated depending on the transcription factor c-Myc (Chen et al, 2015 ). Taking into account that a number of recent studies have identified the role of miRNAs in neurodegenerative disorders, including AD, PD and Huntington's disease (Maciotta et al, 2013 ; da Silva et al, 2016 ; Salta and De Strooper, 2017 ), changes in the miRNA pattern in developing brain after prenatal hypoxia will certainly result in a neurodegeneration-prone phenotype in later life. Quantitative analysis of hypoxia-regulated miRNAs in the maternal blood may provide a tool for identifying risk of fetal hypoxia (Whitehead et al, 2013 ).…”

Section: Epigenetic Consequences Of Prenatal Hypoxiamentioning

confidence: 99%

Role of Prenatal Hypoxia in Brain Development, Cognitive Functions, and Neurodegeneration

2018

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This review focuses on the role of prenatal hypoxia in the development of brain functions in the postnatal period and subsequent increased risk of neurodegenerative disorders in later life. Accumulating evidence suggests that prenatal hypoxia in critical periods of brain formation results in significant changes in development of cognitive functions at various stages of postnatal life which correlate with morphological changes in brain structures involved in learning and memory. Prenatal hypoxia also leads to a decrease in brain adaptive potential and plasticity due to the disturbance in the process of formation of new contacts between cells and propagation of neuronal stimuli, especially in the cortex and hippocampus. On the other hand, prenatal hypoxia has a significant impact on expression and processing of a variety of genes involved in normal brain function and their epigenetic regulation. This results in changes in the patterns of mRNA and protein expression and their post-translational modifications, including protein misfolding and clearance. Among proteins affected by prenatal hypoxia are a key enzyme of the cholinergic system-acetylcholinesterase, and the amyloid precursor protein (APP), both of which have important roles in brain function. Disruption of their expression and metabolism caused by prenatal hypoxia can also result, apart from early cognitive dysfunctions, in development of neurodegeneration in later life. Another group of enzymes affected by prenatal hypoxia are peptidases involved in catabolism of neuropeptides, including amyloid-β peptide (Aβ). The decrease in the activity of neprilysin and other amyloid-degrading enzymes observed after prenatal hypoxia could result over the years in an Aβ clearance deficit and accumulation of its toxic species which cause neuronal cell death and development of neurodegeneration. Applying various approaches to restore expression of neuronal genes disrupted by prenatal hypoxia during postnatal development opens an avenue for therapeutic compensation of cognitive dysfunctions and prevention of Aβ accumulation in the aging brain and the model of prenatal hypoxia in rodents can be used as a reliable tool for assessment of their efficacy.

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microRNAs involved in Parkinson's disease: A systematic review

Cited by 35 publications

References 56 publications

Meta‐analyses identify differentially expressed microRNAs in Parkinson's disease

Meta‐analyses identify differentially expressed microRNAs in Parkinson's disease

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

Role of Prenatal Hypoxia in Brain Development, Cognitive Functions, and Neurodegeneration

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