Circulating nucleic acids in the plasma and serum as potential biomarkers in neurological disorders

Bruno, Danielle do Carmo Ferreira; Donatti, Amanda; Martin, Mariana; Almeida, Vanessa Simão de; Geraldis, Jaqueline Cruz; Oliveira, Fabiana Sodré de; Dogini, D.B.; Lopes-Cendes, Íscia

doi:10.1590/1414-431x20209881

Cited by 23 publications

(24 citation statements)

References 86 publications

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“…Recognized mainly by TLR-9 and STING ( 75 , 105 ), mtDNA has already been shown to be elevated in the serum of patients with ischemic brain injury ( 106 , 107 ). Type I IFNs signaling rely on the interaction with Type I Interferon Receptors (IFNAR) and subsequent intracellular cascades that culminates in the phosphorylation of Jak-STATS and IRFs, and the transcription of Interferon Stimulated Genes (ISGs) ( 100 ).…”

Section: Mitochondrial Damps and Neurodegenerationmentioning

confidence: 99%

Unraveling the Link Between Mitochondrial Dynamics and Neuroinflammation

et al. 2021

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Neuroinflammatory and neurodegenerative diseases are a major public health problem worldwide, especially with the increase of life-expectancy observed during the last decades. For many of these diseases, we still lack a full understanding of their etiology and pathophysiology. Nonetheless their association with mitochondrial dysfunction highlights this organelle as an important player during CNS homeostasis and disease. Markers of Parkinson (PD) and Alzheimer (AD) diseases are able to induce innate immune pathways induced by alterations in mitochondrial Ca2+ homeostasis leading to neuroinflammation. Additionally, exacerbated type I IFN responses triggered by mitochondrial DNA (mtDNA), failures in mitophagy, ER-mitochondria communication and mtROS production promote neurodegeneration. On the other hand, regulation of mitochondrial dynamics is essential for CNS health maintenance and leading to the induction of IL-10 and reduction of TNF-α secretion, increased cell viability and diminished cell injury in addition to reduced oxidative stress. Thus, although previously solely seen as power suppliers to organelles and molecular processes, it is now well established that mitochondria have many other important roles, including during immune responses. Here, we discuss the importance of these mitochondrial dynamics during neuroinflammation, and how they correlate either with the amelioration or worsening of CNS disease.

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Section: Mitochondrial Damps and Neurodegenerationmentioning

confidence: 99%

Unraveling the Link Between Mitochondrial Dynamics and Neuroinflammation

et al. 2021

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“…However, when we performed the metanalysis, we found that such panel are poorly feasible since data have high risk of publication and sampling bias. Despite such observation when data were analyze per subgroup we found that that further studies seeking to characterize miRNA-based biomarkers for AIS diagnosis may be conducted in plasma, since this shows the lowest risk of publishing bias of all the analyzed tissues, as previously reported 33 , 34 .…”

Section: Discussionmentioning

confidence: 67%

Towards a MicroRNAs-Based Biomarker Panel for AIS: A Meta-Analysis

Rivero-Segura¹,

Gómez-Verján²,

Ramírez‐Aldana³

2021

Preprint

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Background: Acute ischemic stroke is among the main causes of mortality worldwide; a rapid and opportune diagnosis is crucial to improve a patient's outcome. MicroRNAs are quite useful for a rapid and accurate diagnosis.Methods: We perform both structural networks approach and a meta-analysis (using a random-effect model to evaluate the heterogeneity and risk bias, according to the PRISMA statement) to analyze the feasibility to develop a microRNA-based biomarker panel for an opportune AIS diagnosis. Results: Structural networks identify a set of eight miRNAs (miR-16, miR-124-3p, miR-484, miR-15a, miR-4454, miR-107, miR-125b-5p and miR-320b) as preliminary microRNA-based biomarker panel, from these only three microRNAs are significantly associated with the main risk factors of AIS, (miR-107: hypertension, 95% CI 9.74-53.24 p<0.0001, type 2 Diabetes mellitus, 95% CI 2.18-19.26); p=0.0008; miR-16 hypertension, 95% CI 1.26-3.56 p=0.0046, smoking, 95% CI 1.07-3.54 p=0.0277; and miR-15a hypertension, 95% CI 1.26-3.56 p=0.0046; smoking, 95% CI 1.07-3.54 p=0.0277). However, the meta-analysis reveals that data is highly heterogeneous and biased; and only microRNAs isolated from plasma samples and further processed in microarrays are the most reliable to distinguish AIS patients.Conclusions: Together our results show that although there are some miRNAs that seem to be associated with AIS, we are still far to develop a miRNA-based biomarker for AIS diagnosis and it is necessary to harmonize the protocols, results and include more populations for further studies otherwise we will remain throwing punches in the dark.

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“…MiRNA levels in peripheral blood reflect the miRNA levels in the central nervous system (CNS) as miRNA and other circulating nucleic acids can cross the blood-brain barrier (BBB) under physiological conditions [ 28 ]. Pathological conditions may disrupt the BBB, which further increases the permeability allowing for the open flow of molecules into the peripheral circulation.…”

Section: Discussionmentioning

confidence: 99%

“…Pathological conditions may disrupt the BBB, which further increases the permeability allowing for the open flow of molecules into the peripheral circulation. This indicates that peripheral blood reflects the level of miRNAs from the CNS [ 28 ]..…”

Section: Discussionmentioning

confidence: 99%

Association of circulating let-7b-5p with major depressive disorder: a nested case-control study

et al. 2021

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Background Major depressive disorder (MDD) is one of the most common psychiatric disorders and is a great disease burden. However, its underlying pathophysiology and aetiology remain poorly understood. Available evidence suggests that circulating microRNAs (miRNAs) are associated with MDD, but it is still unknown whether miRNAs can predict subsequent incident MDD. Methods In this nested case-control study, a total of 104 individuals, who were free of MDD at baseline, from the Women’s Health in Lund Area (WHILA) cohort were included. Among them, 52 individuals developed MDD (cases) during the 5 years follow-up and 52 individuals did not develop MDD (controls). Plasma expression levels of miR-17-5p, miR-134-5p, miR-144-5p, let-7b-5p and let-7c-5p at baseline were assessed using qRT-PCR. Logistic regression was used to estimate the odds of developing MDD among individuals with different levels of miRNA expression. Results Plasma expression levels of let-7b-5p were significantly lower (p = 0.02) at baseline in cases compared to controls. After adjustment for age and BMI, let-7b-5p was negatively associated with odds for developing MDD (OR = 0.33, p = 0.03, 95% CI = 0.12–0.91). Moreover, let-7b-5p expression levels showed a trend over time with larger differences between cases and controls for the earlier cases (MDD diagnosis <2 years from baseline) than MDD cases developed later (MDD diagnosis 2–5 years from baseline). Conclusions These findings show that lower plasma levels of let-7b-5p are associated with a higher future risk of MDD. Results need to be validated in a large cohort to examine its potential as a peripheral biomarker for MDD.

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Circulating nucleic acids in the plasma and serum as potential biomarkers in neurological disorders

Cited by 23 publications

References 86 publications

Unraveling the Link Between Mitochondrial Dynamics and Neuroinflammation

Unraveling the Link Between Mitochondrial Dynamics and Neuroinflammation

Towards a MicroRNAs-Based Biomarker Panel for AIS: A Meta-Analysis

Association of circulating let-7b-5p with major depressive disorder: a nested case-control study

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