MicroRNAs as Biomarkers in Amyotrophic Lateral Sclerosis

Ricci, Claudia; Marzocchi, Carlotta; Battistini, Stefania

doi:10.3390/cells7110219

Cited by 90 publications

(84 citation statements)

References 96 publications

(173 reference statements)

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“…miRNAs have been proposed as promising biomarkers for diagnosis and monitoring progression of various diseases [64], including ALS [37,65]. They have been discovered in many types of body fluids, including plasma, CSF, tears, saliva, colostrum, and peritoneal fluid [66].…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs are small, non-coding RNA fragments that act as epigenetic regulators of gene expression and have been proposed as candidates for biomarkers of several diseases, including neurodegenerative ones [37,38]. Among those related to regulation of processes associated with neuronal cells survival and function, we selected candidates that were previously described as involved in ALS occurrence and disease progression.…”

Section: Introductionmentioning

confidence: 99%

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Local and Systemic Humoral Response to Autologous Lineage-Negative Cells Intrathecal Administration in ALS Patients

Baumert

Sobuś

Gołąb-Janowska

et al. 2020

IJMS

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Amyotrophic lateral sclerosis (ALS) remains a fatal disease with limited therapeutic options. Signaling via neurotrophins (NTs), neuroinflammation, and certain micro-RNAs are believed to play essential role in ALS pathogenesis. Lineage-negative stem/progenitor cells (Lin−) were obtained from bone marrow of 18 ALS patients and administered intrathecally. Clinical assessment was performed using ALS Functional Rating Scale (FRSr) and Norris scale. Protein concentrations were measured in plasma and cerebrospinal fluid (CSF) by multiplex fluorescent bead-based immunoassay. Gene expression in nucleated blood cells was assessed using gene microarray technique. Finally, miRNA expression was analyzed using qPCR in CSF and plasma samples. We observed a significant decrease of C-reactive protein (CRP) concentration in plasma on the seventh day from the application of cells. Gene array results revealed decreased expression of gene sets responsible for neutrophil activation. Further analysis revealed moderate negative correlation between CRP level in CSF and clinical outcome. Brain-derived neurotrophic factor (BDNF) concentrations in both plasma and CSF significantly correlated with the favorable clinical outcome. On a micro-RNA level, we observed significant increase of miR-16-5p expression one week after transplantation in both body fluids and significant increase of miR-206 expression in plasma. Administration of Lin− cells may decrease inflammatory response and prevent neurodegeneration. However, these issues require further investigations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Local and Systemic Humoral Response to Autologous Lineage-Negative Cells Intrathecal Administration in ALS Patients

Baumert

Sobuś

Gołąb-Janowska

et al. 2020

IJMS

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“…Both can directly reduce the level of NCKAP1 expression [48,49], in agreement with our results. Speci cally, miRNA-214-3p expression was increased in microglia isolated from SOD1-G93A mice [65] and in muscles [66] and sera [67] of ALS patients. This miRNA acts as an in ammatory mediator that induces NF-κB activation and IL-6 expression [68].…”

Section: Discussionmentioning

confidence: 93%

Defective phagocytic function of induced microglia-like cells is correlated with rapid progression of sporadic ALS

Noh¹,

Kwon²,

Oh³

et al. 2020

Preprint

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Background: Microglia play a key role in determining the progression of amyotrophic lateral sclerosis (ALS), yet their precise role in ALS has not been identified in humans. The objective of this study was to identify the functional characteristics of microglia and related factors in patients with sporadic ALS that is rapidly progressing.Methods: After confirming that microglia-like cells (iMGs) induced by human monocytes could recapitulate the main signatures of brain microglia, serial comparative studies were conducted to delineate functional differences in iMGs from patients with slowly progressive ALS [ALS(S), n = 14] versus rapidly progressive ALS [ALS(R), n = 15].Results: Despite an absence of significant differences in the expression of microglial homeostatic genes, ALS(R)-iMGs preferentially showed defective phagocytosis and an exaggerated pro-inflammatory response to LPS stimuli compared to ALS(S)-iMGs. Transcriptome analysis revealed that the perturbed phagocytosis seen in ALS(R)-iMGs was closely associated with decreased NCKAP1 (NCK-associated protein 1)-mediated abnormal actin polymerization. NCKAP1 overexpression was sufficient to rescue impaired phagocytosis in ALS(R)-iMGs. To leverage our findings and identify biological markers of rapidly progressing ALS, we measured plasma miRNA-214-3p (negative regulator targeting NCKAP1) levels. Post-hoc analysis indicated that decreased NCKAP1 expression in iMGs and a concomitant increase in plasma miRNA-214-3p levels was correlated with rapid progression of ALS.Interpretation: Our data suggest that microglial NCKAP1 may be an alternative therapeutic target in rapidly progressive sporadic ALS. In addition, miRNA-214-3p levels could be a serological biomarker for predicting the speed of disease progression.

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“…Despite this, a number of effective CmiRNAs detection methods have been developed in recent years, including not only traditional cDNA library cloning, Northern blot and qRT-PCR, but also newly developed gene chip technology, highthroughput sequencing and nanostring nCounter (Morozova and Marra, 2008;Roberts et al, 2014;Ricci et al, 2018). With the development of molecular biology technology, the detection methods for CmiRNAs have been improved and developed, the new technologies enable the detection of CmiRNAs with greater sensitivity and precision, providing technical support for CmiRNAs to become diagnostic biomarkers (Figure 1).…”

Section: Source Existence Extraction and Detection Of Mirnas And Tmentioning

confidence: 99%

Circulating MicroRNAs as Diagnostic Biomarkers for Motor Neuron Disease

Lin

Zhang

2020

Front. Neurosci.

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Motor neuron disease (MND) is a kind of neurodegenerative disease that selectively invades spinal cord anterior horn cells, brainstem motor neurons, cortical pyramidal cells and the pyramidal tract. The main clinical features are the symptoms and signs of impaired upper and lower motor neurons, manifested as muscle weakness, atrophy and pyramidal tract signs. Histopathology has shown the disappearance of pyramidal cells in the motor cortex, loss of motor neurons in the anterior horn of the spinal cord and brainstem, and degeneration of the corticospinal tract. Due to the lack of effective treatment methods, the prognosis is generally poor, so it is of great significance to confirm the diagnosis early by various means. However, the current diagnosis of MND mainly relies on the combination of clinical manifestations and neurophysiological examinations, lacking effective means of early diagnosis. Circulating microRNA (CmiRNA) is a kind of stable miRNA molecule in serum, plasma and other body fluids, which has the characteristics of distinct differential expression, sensitive detection and convenient sample collection. As a possible new biomarker of MND, CmiRNA can not only reveal the pathophysiological process of MND, but also monitor disease progression and response to drug therapy. With the development of miRNA detection technology, more and more CmiRNAs as biomarkers with potential diagnostic value have been investigated. In this review, we explored the possibility of circulating samples as different sources of biomarkers for the diagnosis of MND, analyzing the progress of CmiRNA detection techniques, and presenting potential diagnostic MND biomarkers that have been reported.

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MicroRNAs as Biomarkers in Amyotrophic Lateral Sclerosis

Cited by 90 publications

References 96 publications

Local and Systemic Humoral Response to Autologous Lineage-Negative Cells Intrathecal Administration in ALS Patients

Local and Systemic Humoral Response to Autologous Lineage-Negative Cells Intrathecal Administration in ALS Patients

Defective phagocytic function of induced microglia-like cells is correlated with rapid progression of sporadic ALS

Circulating MicroRNAs as Diagnostic Biomarkers for Motor Neuron Disease

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