MicroRNA: Basic concepts and implications for regeneration and repair of neurodegenerative diseases

Saraiva, Cláudia; Esteves, Marta; Bernardino, Liliana

doi:10.1016/j.bcp.2017.07.008

Cited by 59 publications

(41 citation statements)

References 203 publications

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“…miRNAs are small non-coding RNA molecules that regulate at the post-transcriptional level the expression of genes involved in cellular response to stressors and other pathogenic insults (Viader et al, 2011; Kye and Goncalves Ido, 2014). Interestingly, despite being found rapidly degraded in post-mortem brain tissue, miRNAs are stable in serum and other body fluids, such as CSF (Saraiva et al, 2017). Therefore their evaluation can be informative in healthy as in pathological conditions.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of Patients With Sporadic Amyotrophic Lateral Sclerosis

Liguori

Nuzziello

Introna

et al. 2018

Front. Mol. Neurosci.

104

106

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Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease. While genetics and other factors contribute to ALS pathogenesis, critical knowledge is still missing and validated biomarkers for monitoring the disease activity have not yet been identified. To address those aspects we carried out this study with the primary aim of identifying possible miRNAs/mRNAs dysregulation associated with the sporadic form of the disease (sALS). Additionally, we explored miRNAs as modulating factors of the observed clinical features. Study included 56 sALS and 20 healthy controls (HCs). We analyzed the peripheral blood samples of sALS patients and HCs with a high-throughput next-generation sequencing followed by an integrated bioinformatics/biostatistics analysis. Results showed that 38 miRNAs (let-7a-5p, let-7d-5p, let-7f-5p, let-7g-5p, let-7i-5p, miR-103a-3p, miR-106b-3p, miR-128-3p, miR-130a-3p, miR-130b-3p, miR-144-5p, miR-148a-3p, miR-148b-3p, miR-15a-5p, miR-15b-5p, miR-151a-5p, miR-151b, miR-16-5p, miR-182-5p, miR-183-5p, miR-186-5p, miR-22-3p, miR-221-3p, miR-223-3p, miR-23a-3p, miR-26a-5p, miR-26b-5p, miR-27b-3p, miR-28-3p, miR-30b-5p, miR-30c-5p, miR-342-3p, miR-425-5p, miR-451a, miR-532-5p, miR-550a-3p, miR-584-5p, miR-93-5p) were significantly downregulated in sALS. We also found that different miRNAs profiles characterized the bulbar/spinal onset and the progression rate. This observation supports the hypothesis that miRNAs may impact the phenotypic expression of the disease. Genes known to be associated with ALS (e.g., PARK7, C9orf72, ALS2, MATR3, SPG11, ATXN2) were confirmed to be dysregulated in our study. We also identified other potential candidate genes like LGALS3 (implicated in neuroinflammation) and PRKCD (activated in mitochondrial-induced apoptosis). Some of the downregulated genes are involved in molecular bindings to ions (i.e., metals, zinc, magnesium) and in ions-related functions. The genes that we found upregulated were involved in the immune response, oxidation–reduction, and apoptosis. These findings may have important implication for the monitoring, e.g., of sALS progression and therefore represent a significant advance in the elucidation of the disease’s underlying molecular mechanisms. The extensive multidisciplinary approach we applied in this study was critically important for its success, especially in complex disorders such as sALS, wherein access to genetic background is a major limitation.

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Section: Introductionmentioning

confidence: 99%

Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of Patients With Sporadic Amyotrophic Lateral Sclerosis

Liguori

Nuzziello

Introna

et al. 2018

Front. Mol. Neurosci.

104

106

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“…This miR also plays a key role regulating synaptic plasticity and memory signaling molecules (Fischbach and Carew, 2009). MiR-124 is also highly expressed in microglia, where it takes part in the regulation of microglia quiescence (Ponomarev et al, 2011;Saraiva et al, 2017).…”

Section: Mir Functionmentioning

confidence: 99%

MiR-124 and the Underlying Therapeutic Promise of Neurodegenerative Disorders

et al. 2020

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Neurodegenerative disorders (NDDs) are a group of chronic progressive neurological diseases based on primary neurodegeneration. The common pathological characteristics of various NDDs are neuronal degeneration, deletion, glial cell proliferation, and hypertrophy at specific locations in the nervous system. Proliferation and hypertrophy of microglia are manifestations of inflammation. MicroRNAs (miRNAs) have emerged as pivotal regulators of glial cells. MiRNAs are small non-coding molecules that regulate gene expression. Altered expression of miRNAs has been associated with several NDD pathological processes, among which regulation of the inflammatory response is key and a research hotspot at present. At the same time, miRNAs are also biological markers for diagnosis and potential targets for treating NDDs. MiR-124 is highly conserved and enriched in the mammalian brain. Emerging studies have suggested that miR-124 is closely related to the pathogenesis of NDDs and may be an effective treatment strategy to reduce inflammation associated with NDDs. In this review, we describe a summary of general miRNA biology, implications in pathophysiology, the potential roles of miR-124 associated with inflammation, and the use of miRNA as a future biomarker and an application for NDD therapy.

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“…One mature single-stranded miRNA remains in the complex, and the complementary mRNA sites regulate gene expression through base pairing (Higa et al, 2014). miRNAs in the nervous system constitute a complex network for regulating gene expression that plays an important role in the normal physiological regulation of the nervous system and the progression of NDDs (Properzi et al, 2015;Saraiva et al, 2017). The distribution of miRNAs into exosomes in the cytoplasm can be regulated by a variety of mechanisms.…”

Section: Exosome Composition and Mirna Synthesis And Packagingmentioning

confidence: 99%

Circulating Exosomal miRNA as Diagnostic Biomarkers of Neurodegenerative Diseases

Wang

Zhang

2020

Front. Mol. Neurosci.

106

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Neurodegenerative diseases (NDDs) are a group of diseases caused by chronic and progressive degeneration of neural tissue. The main pathological manifestations are neuronal degeneration and loss in the brain and/or spinal cord. Common NDDs include Alzheimer disease (AD), Parkinson disease (PD), Huntington disease (HD), and amyotrophic lateral sclerosis (ALS). The complicated pathological characteristics and different clinical manifestations of NDDs result in a lack of sensitive and efficient diagnostic methods. In addition, no sensitive biomarkers are available to monitor the course of NDDs, predict their prognosis, and monitor the therapeutic response. Despite extensive research in recent years, analysis of amyloid β (Aβ) and α-synuclein has failed to effectively improve NDD diagnosis. Although recent studies have indicated circulating miRNAs as promising diagnostic biomarkers of NDDs, the miRNA in the peripheral circulation is susceptible to interference by other components, making circulating miRNA results less consistent. Exosomes are small membrane vesicles with a diameter of approximately 30-100 nm that transport proteins, lipids, mRNA, and miRNA. Because recent studies have shown that exosomes have a double-membrane structure that can resist ribonuclease in the blood, giving exosomal miRNA high stability and making them resistant to degradation, they may become an ideal biomarker of circulating fluids. In this review, we discuss the applicability of circulating exosomal miRNAs as biomarkers, highlight the technical aspects of exosomal miRNA analysis, and review studies that have used circulating exosomal miRNAs as candidate diagnostic biomarkers of NDDs.

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MicroRNA: Basic concepts and implications for regeneration and repair of neurodegenerative diseases

Cited by 59 publications

References 203 publications

Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of Patients With Sporadic Amyotrophic Lateral Sclerosis

Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of Patients With Sporadic Amyotrophic Lateral Sclerosis

MiR-124 and the Underlying Therapeutic Promise of Neurodegenerative Disorders

Circulating Exosomal miRNA as Diagnostic Biomarkers of Neurodegenerative Diseases

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