The role of miRNA in motor neuron disease

Kye, Min Jeong; Gonçalves, Inês do Carmo G.

doi:10.3389/fncel.2014.00015

Cited by 50 publications

(55 citation statements)

References 98 publications

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“…Of particular interest, miRNA dysregulation is linked to aging and neurodegenerative disorders, including PD, AD, and multiple sclerosis (Goodall et al, 2013; Li et al, 2011; Ma et al, 2014). miRNA alterations are also present in microglial and neuronal cells in rodent ALS models and in peripheral blood mononuclear cells (PBMCs), fibroblasts, cerebrospinal fluid, and postmortem tissue from ALS subjects (Butovsky et al, 2012; Campos-Melo et al, 2013; De Felice et al, 2012; Freischmidt et al, 2014; Koval et al, 2013a; Kye and Goncalves Ido, 2014; Shinde et al, 2013), results which all support our observed DEmiRNAs in postmortem ALS spinal cord tissue. DEmiRNAs are likewise present in serum from pre-manifest fALS mutation carriers, suggesting both a role for miRNAs in ALS pathogenesis and as potential diagnostic biomarkers (Freischmidt et al, 2014).…”

Section: Discussionsupporting

confidence: 85%

Expression of microRNAs in human post-mortem amyotrophic lateral sclerosis spinal cords provides insight into disease mechanisms

Figueroa‐Romero

Hur

Lunn

et al. 2016

Molecular and Cellular Neuroscience

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Amyotrophic lateral sclerosis is a late-onset and terminal neurodegenerative disease. The majority of cases are sporadic with unknown causes and only a small number of cases are genetically linked. Recent evidence suggests that post-transcriptional regulation and epigenetic mechanisms, such as microRNAs, underlie the onset and progression of neurodegenerative disorders; therefore, altered microRNA expression may result in the dysregulation of key genes and biological pathways that contribute to the development of sporadic amyotrophic lateral sclerosis. Using systems biology analyses on postmortem human spinal cord tissue, we identified dysregulated mature microRNAs and their potential targets previously implicated in functional process and pathways associated with the pathogenesis of ALS. Furthermore, we report a global reduction of mature microRNAs, alterations in microRNA processing, and support for a role of the nucleotide binding protein, TAR DNA binding protein 43, in regulating sporadic amyotrophic lateral sclerosis-associated microRNAs, thereby offering a potential underlying mechanism for sporadic amyotrophic lateral sclerosis.

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Section: Discussionsupporting

confidence: 85%

Expression of microRNAs in human post-mortem amyotrophic lateral sclerosis spinal cords provides insight into disease mechanisms

Figueroa‐Romero

Hur

Lunn

et al. 2016

Molecular and Cellular Neuroscience

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“…The proinflammatory cytokine IL-6 was examined as an indicator of microglial cell function. The chemokine, fractalkine (CX3CL1) and its cognate receptor (CX3CR1) were also analyzed, as recent evidence suggests that neuronally expressed CX3CL1 can modulate glutamatergic tone, inhibit microglial cell activation, and regulate the effects of chronic stress on neuronal plasticity and depressive-like behaviors through microglial CX3CR1-mediated actions (Paolicelli et al, 2014; Sheridan et al, 2014; Milior et al, 2015). …”

Section: Methodsmentioning

confidence: 99%

Differential effects of stress on microglial cell activation in male and female medial prefrontal cortex

Bollinger

Burns

Wellman

2016

Brain, Behavior, and Immunity

181

122

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Susceptibility to stress-linked psychological disorders, including post-traumatic stress disorder and depression, differs between men and women. Dysfunction of medial prefrontal cortex (mPFC) has been implicated in many of these disorders. Chronic stress affects mPFC in a sex-dependent manner, differentially remodeling dendritic morphology and disrupting prefrontally mediated behaviors in males and females. Chronic restraint stress induces microglial activation, reflected in altered microglial morphology and immune factor expression, in mPFC in male rats. Unstressed females exhibit increased microglial ramification in several brain regions compared to males, suggesting both heightened basal activation and a potential for sex-dependent effects of stress on microglial activation. Therefore, we assessed microglial density and ramification in the prelimbic region of mPFC, and immune-associated genes in dorsal mPFC in male and female rats following acute or chronic restraint stress. Control rats were left unstressed. On the final day of restraint, brains were collected for either qPCR or visualization of microglia using Iba-1 immunohistochemistry. Microglia in mPFC were classified as ramified, primed, reactive, or amoeboid, and counted stereologically. Expression of microglia-associated genes (MHCII, CD40, IL6, CX3CL1, and CX3CR1) was also assessed using qPCR. Unstressed females showed a greater proportion of primed to ramified microglia relative to males, alongside heightened CX3CL1-CX3CR1 expression. Acute and chronic restraint stress reduced the proportion of primed to ramified microglia and microglial CD40 expression in females, but did not significantly alter microglial activation in males. This sex difference in microglial activation could contribute to the differential effects of stress on mPFC structure and function in males versus females.

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“…In addition, mutant TDP-43 and FUS proteins may also contribute to ALS pathology by affecting the biogenesis of microRNAs, which are known to have an important role in motor neuron and NMJ function (Williams et al, 2009; Kye and Gonçalves Ido, 2014). …”

Section: Theories On the Cause(s) Of Salsmentioning

confidence: 99%

ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease

2014

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Amyotrophic Lateral Sclerosis (ALS) is being redefined as a distal axonopathy, in that many molecular changes influencing motor neuron degeneration occur at the neuromuscular junction (NMJ) at very early stages of the disease prior to symptom onset. A huge variety of genetic and environmental causes have been associated with ALS, and interestingly, although the cause of the disease can differ, both sporadic and familial forms of ALS show a remarkable similarity in terms of disease progression and clinical manifestation. The NMJ is a highly specialized synapse, allowing for controlled signaling between muscle and nerve necessary for skeletal muscle function. In this review we will evaluate the clinical, animal experimental and cellular/molecular evidence that supports the idea of ALS as a distal axonopathy. We will discuss the early molecular mechanisms that occur at the NMJ, which alter the functional abilities of the NMJ. Specifically, we focus on the role of axon guidance molecules on the stability of the cytoskeleton and how these molecules may directly influence the cells of the NMJ in a way that may initiate or facilitate the dismantling of the neuromuscular synapse in the presymptomatic stages of ALS.

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The role of miRNA in motor neuron disease

Cited by 50 publications

References 98 publications

Expression of microRNAs in human post-mortem amyotrophic lateral sclerosis spinal cords provides insight into disease mechanisms

Expression of microRNAs in human post-mortem amyotrophic lateral sclerosis spinal cords provides insight into disease mechanisms

Differential effects of stress on microglial cell activation in male and female medial prefrontal cortex

ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease

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