MicroRNA Metabolism and Dysregulation in Amyotrophic Lateral Sclerosis

Rinchetti, Paola; Rizzuti, Mafalda; Faravelli, Irene; Corti, Stefania

doi:10.1007/s12035-017-0537-z

Cited by 56 publications

(40 citation statements)

References 176 publications

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“…miRNAs have a tissue-specific expression and this knowledge can help to better understand a normal and a disease development of the respective tissue [ 23 ]. miRNAs are known to play important roles in many physiological and pathological processes, including tumorigenesis [ 24 ], metabolism [ 25 ], immune function [ 26 ], and several neurodegenerative disorders [ 27 ], such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease [ 28 ] and also ALS [ 29 ].…”

Section: Mirnas As Biomarkersmentioning

confidence: 99%

MicroRNAs as Biomarkers in Amyotrophic Lateral Sclerosis

Ricci

Marzocchi

Battistini

2018

Cells

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Amyotrophic lateral sclerosis (ALS) is an incurable and fatal disorder characterized by the progressive loss of motor neurons in the cerebral cortex, brain stem, and spinal cord. Sporadic ALS form accounts for the majority of patients, but in 1–13.5% of cases the disease is inherited. The diagnosis of ALS is mainly based on clinical assessment and electrophysiological examinations with a history of symptom progression and is then made with a significant delay from symptom onset. Thus, the identification of biomarkers specific for ALS could be of a fundamental importance in the clinical practice. An ideal biomarker should display high specificity and sensitivity for discriminating ALS from control subjects and from ALS-mimics and other neurological diseases, and should then monitor disease progression within individual patients. microRNAs (miRNAs) are considered promising biomarkers for neurodegenerative diseases, since they are remarkably stable in human body fluids and can reflect physiological and pathological processes relevant for ALS. Here, we review the state of the art of miRNA biomarker identification for ALS in cerebrospinal fluid (CSF), blood and muscle tissue; we discuss advantages and disadvantages of different approaches, and underline the limits but also the great potential of this research for future practical applications.

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Section: Mirnas As Biomarkersmentioning

confidence: 99%

MicroRNAs as Biomarkers in Amyotrophic Lateral Sclerosis

Ricci

Marzocchi

Battistini

2018

Cells

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“…Several miRNAs required for synaptic development and maintenance including miR-9 and miR-124 were found to be altered in ALS/FTD patient derived cells and tissues suggesting the possibility that specific miRNAs may mediate aspects of toxicity in disease [92, 93]. Although the precise role of miRNAs in disease remains unclear, existing evidence supports the possibility of both a global and target-specific inhibition of miRNA synthesis as a contributor to ALS/FTD pathogenesis (recently reviewed in [91, 94]).…”

Section: Micro Rnas (Mirnas) and Translation Regulationmentioning

confidence: 99%

Lost in Translation: Evidence for Protein Synthesis Deficits in ALS/FTD and Related Neurodegenerative Diseases

Lehmkuhl

Zarnescu

2018

Advances in Neurobiology

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Cells utilize a complex network of proteins to regulate translation, involving post-transcriptional processing of RNA and assembly of the ribosomal unit. Although the complexity provides robust regulation of proteostasis, it also offers several opportunities for translational dysregulation, as has been observed in many neurodegenerative disorders. Defective mRNA localization, mRNA sequatration, inhibited ribogenesis, mutant tRNA synthetases, and translation of hexanucleotide expansions have all been associated with neurodegenerative disease. Here, we review dysregulation of translation in the context of age-related neurodegeneration and discuss novel methods to interrogate translation. This review primarily focuses on amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a spectrum disorder heavily associated with RNA metabolism, while also analyzing translational inhibition in the context of related neurodegenerative disorders such as Alzheimer's disease and Huntington's disease and the translation-related pathomechanisms common in neurodegenerative disease.

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“…; Rinchetti et al . ). MiR‐124 is expressed in the nervous system and is one of the most abundant miRNAs in the brain.…”

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confidence: 97%

Screening the expression characteristics of several miRNAs in G93A‐SOD1 transgenic mouse: altered expression of miRNA‐124 is associated with astrocyte differentiation by targeting Sox2 and Sox9

Zhou

Zhang

Guan

et al. 2017

Journal of Neurochemistry

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MicroRNAs (miRNAs) are suspected to be a contributing factor in amyotrophic lateral sclerosis (ALS). Here, we assess the altered expression of miRNAs and the effects of miR-124 in astrocytic differentiation in neural stem cells of ALS transgenic mice. Differentially expressed miRNA-positive cells (including miR-124, miR-181a, miR-22, miR-26b, miR-34a, miR-146a, miR-219, miR-21, miR-200a, and miR-320) were detected by in situ hybridization and qRT-PCR in the spinal cord and the brainstem. Our results demonstrated that miR-124 was down-regulated in the spinal cord and brainstem. In vitro, miR-124 was down-regulated in neural stem cells and up-regulated in differentiated neural stem cells in G93A-superoxide dismutase 1 (SOD1) mice compared with WT mice by qRT-PCR. Meanwhile, Sox2 and Sox9 protein levels showed converse change with miR-124 in vivo and vitro. After over-expression or knockdown of miR-124 in motor neuron-like hybrid (NSC34) cells of mouse, Sox2 and Sox9 proteins were noticeably down-regulated or up-regulated, whereas Sox2 and Sox9 mRNAs remained virtually unchanged. Moreover, immunofluorescence results indicated that the number of double-positive cells of Sox2/glial fibrillary acidic protein (GFAP) and Sox9/glial fibrillary acidic protein (GFAP) was higher in G93A-SOD1 mice compared with WT mice. We also found that many Sox2- and Sox9-positive cells were nestin positive in G93A-SOD1 mice, but not in WT mice. Furthermore, differentiated neural stem cells from G93A-SOD1 mice generated a greater proportion of astrocytes and lower proportion of neurons than those from WT mice. MiR-124 may play an important role in astrocytic differentiation by targeting Sox2 and Sox9 in ALS transgenic mice. Cover Image for this issue: doi: 10.1111/jnc.14171.

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MicroRNA Metabolism and Dysregulation in Amyotrophic Lateral Sclerosis

Cited by 56 publications

References 176 publications

MicroRNAs as Biomarkers in Amyotrophic Lateral Sclerosis

MicroRNAs as Biomarkers in Amyotrophic Lateral Sclerosis

Lost in Translation: Evidence for Protein Synthesis Deficits in ALS/FTD and Related Neurodegenerative Diseases

Screening the expression characteristics of several miRNAs in G93A‐SOD1 transgenic mouse: altered expression of miRNA‐124 is associated with astrocyte differentiation by targeting Sox2 and Sox9

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