Circulating RNAs as Potential Biomarkers in Amyotrophic Lateral Sclerosis

Ravnik‐Glavač, Metka; Glavač, Damjan

doi:10.3390/ijms21051714

Cited by 53 publications

(42 citation statements)

References 181 publications

(209 reference statements)

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“…Few miRNAs, previously identified from other research groups up-regulated in ALS patients (e.g. miR-338-3p, miR-206 and miR-133 [25][26][27][28] ), were not detected by the analysis of the sequencing data probably because in terms of absolute quantities they are less expressed and therefore more difficult to be detected through NGS. Among them, we decided to analyze the expression of two important myomiR such as miR-206 and miR-133a.…”

Section: Discussionmentioning

confidence: 90%

A longitudinal study defined circulating microRNAs as reliable biomarkers for disease prognosis and progression in ALS human patients

et al. 2021

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with motor neuron degeneration, muscle atrophy and paralysis. To date, multiple panels of biomarkers have been described in ALS patients and murine models. Nevertheless, none of them has sufficient specificity and thus the molecular signature for ALS prognosis and progression remains to be elucidated. Here we overcome this limitation through a longitudinal study, analyzing serum levels of circulating miRNAs, stable molecules that are recently used as promising biomarkers for many types of human disorders, in ALS patients during the progression of the pathology. We performed next-generation sequencing (NGS) analysis and absolute RT quantification of serum samples of ALS patients and healthy controls. The expression levels of five selected miRNAs were quantitatively analyzed during disease progression in each patient and we demonstrated that high levels of miR-206, miR-133a and miR-151a-5p can predict a slower clinical decline of patient functionality. In particular, we found that miR-206 and miR-151a-5p serum levels were significantly up-regulated at the mild stage of ALS pathology, to decrease in the following moderate and severe stages, whereas the expression levels of miR-133a and miR-199a-5p remained low throughout the course of the disease, showing a diagnostic significance in moderate and severe stages for miR-133a and in mild and terminal ones for miR-199a-5p. Moreover, we found that miR-423–3p and 151a-5p were significantly downregulated respectively in mild and terminal stages of the disease. These data suggest that these miRNAs represent potential prognostic markers for ALS disease.

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Section: Discussionmentioning

confidence: 90%

A longitudinal study defined circulating microRNAs as reliable biomarkers for disease prognosis and progression in ALS human patients

et al. 2021

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“…Studies of miRNAs in ALS have been centered in biomarker discovery [232][233][234][235][236][237] and miRNA activity manipulation for therapeutic designs [234,236,238,239]. For example, miR-27a, miR-34a, miR-155, miR-142-5p, and miR-338-3p have been proposed as biomarkers and potential ALS therapeutic targets, directly or indirectly involved in OS [234,236,238,239].…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Non-Coding RNAs as Sensors of Oxidative Stress in Neurodegenerative Diseases

et al. 2020

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Oxidative stress (OS) results from an imbalance between the production of reactive oxygen species and the cellular antioxidant capacity. OS plays a central role in neurodegenerative diseases, where the progressive accumulation of reactive oxygen species induces mitochondrial dysfunction, protein aggregation and inflammation. Regulatory non-protein-coding RNAs (ncRNAs) are essential transcriptional and post-transcriptional gene expression controllers, showing a highly regulated expression in space (cell types), time (developmental and ageing processes) and response to specific stimuli. These dynamic changes shape signaling pathways that are critical for the developmental processes of the nervous system and brain cell homeostasis. Diverse classes of ncRNAs have been involved in the cell response to OS and have been targeted in therapeutic designs. The perturbed expression of ncRNAs has been shown in human neurodegenerative diseases, with these changes contributing to pathogenic mechanisms, including OS and associated toxicity. In the present review, we summarize existing literature linking OS, neurodegeneration and ncRNA function. We provide evidences for the central role of OS in age-related neurodegenerative conditions, recapitulating the main types of regulatory ncRNAs with roles in the normal function of the nervous system and summarizing up-to-date information on ncRNA deregulation with a direct impact on OS associated with major neurodegenerative conditions.

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“…[57][58][59][60] Associations between SMA and miRNAs MiRNAs associated with the pathogenesis of ALS have been studied extensively and reviewed systemically elsewhere. [61][62][63] On the other hand, miR-NAs have been linked to SMA pathogenesis increasingly in studies that suggest miRNAs might act as (1) an essential modulator of SMNmediated molecular pathways; (2) applicable biomarkers representing SMA progress or treatment response; (3) potential therapeutic targets for SMA. 39,55,64 The hypothesis for the link between miRNA and SMA might elucidate the diverse pathways affected by SMN deficiency.…”

Section: The Role Of Mirnas In Motor Neuron Development Survival Anmentioning

confidence: 99%

“… 30 , 142 , 143 In ALS patients, altered miRNA expression has been reported in human specimens of spinal cord, brain, induced pluripotent stem cells (iPSC), muscle, serum, and CSF. 63 , 144 Recently, miRNAs have also been proposed as potential biomarkers in several clinical trials for neuromuscular disorders. 145 – 148 As SMN is known to be involved in miRNA expression, and it entails circulating miRNAs as diagnostic or prognostic biomarkers to reflect the SMA pathology per se or therapeutic effects ( Figure 3 ).…”

Section: Mirna As Circulating Biomarkers For Smamentioning

confidence: 99%

Circulating microRNAs as potential biomarkers and therapeutic targets in spinal muscular atrophy

Chen

2020

Ther Adv Neurol Disord

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Spinal muscular atrophy (SMA), a leading genetic cause of infant death, is a neurodegenerative disease characterized by the selective loss of particular groups of motor neurons (MNs) in the anterior horn of the spinal cord with progressive muscle wasting. SMA is caused by a deficiency of the survival motor neuron (SMN) protein due to a homozygous deletion or mutation of the SMN1 gene. However, the molecular mechanisms whereby the SMN complex regulates MN functions are not fully elucidated. Emerging studies on SMA pathogenesis have turned the attention of researchers to RNA metabolism, given that increasingly identified SMN-associated modifiers are involved in both coding and non-coding RNA (ncRNA) processing. Among various ncRNAs, microRNAs (miRNAs) are the most studied in terms of regulation of posttranscriptional gene expression. Recently, the discovery that miRNAs are critical to MN function and survival led to the study of dysregulated miRNAs in SMA pathogenesis. Circulating miRNAs have drawn attention as a readily available biomarker due to their property of being clinically detectable in numerous human biofluids through non-invasive approaches. As there are recent promising findings from novel miRNA-based medicines, this article presents an extensive review of the most up-to-date studies connecting specific miRNAs to SMA pathogenesis and the potential applications of miRNAs as biomarkers and therapeutic targets for SMA.

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Circulating RNAs as Potential Biomarkers in Amyotrophic Lateral Sclerosis

Cited by 53 publications

References 181 publications

A longitudinal study defined circulating microRNAs as reliable biomarkers for disease prognosis and progression in ALS human patients

A longitudinal study defined circulating microRNAs as reliable biomarkers for disease prognosis and progression in ALS human patients

Non-Coding RNAs as Sensors of Oxidative Stress in Neurodegenerative Diseases

Circulating microRNAs as potential biomarkers and therapeutic targets in spinal muscular atrophy

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