scholarly journals miRNAs in Microglia: Important Players in Multiple Sclerosis Pathology

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142098118
Author(s):  
Alexander D. Walsh ◽  
Linda T. Nguyen ◽  
Michele D. Binder
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Approaches ◽  
Ribonucleic Acids ◽  
Microglial Phagocytosis ◽  
The Central Nervous System ◽  
And Function ◽  
Ms Pathogenesis

Microglia are the resident immune cells of the central nervous system and important regulators of brain homeostasis. Central to this role is a dynamic phenotypic plasticity that enables microglia to respond to environmental and pathological stimuli. Importantly, different microglial phenotypes can be both beneficial and detrimental to central nervous system health. Chronically activated inflammatory microglia are a hallmark of neurodegeneration, including the autoimmune disease multiple sclerosis (MS). By contrast, microglial phagocytosis of myelin debris is essential for resolving inflammation and promoting remyelination. As such, microglia are being explored as a potential therapeutic target for MS. MicroRNAs (miRNAs) are short non-coding ribonucleic acids that regulate gene expression and act as master regulators of cellular phenotype and function. Dysregulation of certain miRNAs can aberrantly activate and promote specific polarisation states in microglia to modulate their activity in inflammation and neurodegeneration. In addition, miRNA dysregulation is implicated in MS pathogenesis, with circulating biomarkers and lesion specific miRNAs identified as regulators of inflammation and myelination. However, the role of miRNAs in microglia that specifically contribute to MS progression are still largely unknown. miRNAs are being explored as therapeutic agents, providing an opportunity to modulate microglial function in neurodegenerative diseases such as MS. This review will focus firstly on elucidating the complex role of microglia in MS pathogenesis. Secondly, we explore the essential roles of miRNAs in microglial function. Finally, we focus on miRNAs that are implicated in microglial processes that contribute directly to MS pathology, prioritising targets that could inform novel therapeutic approaches to MS.

scholarly journals Hyperhomocysteinemia and Endothelial Dysfunction in Multiple Sclerosis

2020 ◽  
Vol 10 (9) ◽  
pp. 637
Author(s):  
Ekaterina Dubchenko ◽  
Alexander Ivanov ◽  
Natalia Spirina ◽  
Nina Smirnova ◽  
Mikhail Melnikov ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Endothelial Dysfunction ◽  
Pleiotropic Effect ◽  
Important Condition ◽  
Leading Role ◽  
The Central Nervous System ◽  
Ms Pathogenesis

Endothelial dysfunction is recognized as one of the leading factors in the pathogenesis of diseases of the central nervous system of various etiologies. Numerous studies have shown the role of hyperhomocysteinemia in the development of endothelial dysfunction and the prothrombogenic state. The most important condition in the development of multiple sclerosis (MS) is a dysregulation of the blood-brain barrier (BBB) and transendothelial leukocyte migration. It has been proven that homocysteine also contributes to the damage of neurons by the mechanism of excitotoxicity and the induction of the apoptosis of neurons. These processes can be one of the factors of neurodegenerative brain damage, which plays a leading role in the progression of MS. This review describes the pleiotropic effect of homocysteine on these processes and its role in MS pathogenesis.

Role of inflammation and apoptosis in multiple sclerosis: Comparative analysis between the periphery and the central nervous system

2015 ◽  
Vol 287 ◽  
pp. 80-87 ◽  
Author(s):  
Beatrice Macchi ◽  
Francesca Marino-Merlo ◽  
Ugo Nocentini ◽  
Valerio Pisani ◽  
Salvatore Cuzzocrea ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Comparative Analysis ◽  
The Central Nervous System

scholarly journals A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2340
Author(s):  
Hannah E. Henson ◽  
Michael R. Taylor
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Developmental Defects ◽  
Whole Exome ◽  
The Central Nervous System ◽  
And Function ◽  
Upregulated Genes ◽  
The Brain

The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a spliceosome protein U4/U6.U5 tri-snRNP-associated protein 1, or Squamous cell carcinoma antigen recognized by T-cells (Sart1). Sart1 recruits the U4.U6/U5 tri-snRNP complex to nuclear RNA. The complex then associates with U1 and U2 snRNPs to form the spliceosome. A forward genetic screen identifying defects in choroid plexus development and whole-exome sequencing (WES) identified a point mutation in exon 12 of sart1 in Danio rerio (zebrafish). This mutation caused an up-regulation of sart1. Using RNA-Seq analysis, we identified additional upregulated genes, including those involved in apoptosis. We also observed increased activated caspase 3 in the brain and eye and down-regulation of vision-related genes. Although splicing occurs in numerous cells types, sart1 expression in zebrafish was restricted to the brain. By identifying sart1 expression in the brain and cell death within the central nervous system (CNS), we provide additional insights into the role of sart1 in specific tissues. We also characterized sart1’s involvement in cell death and vision-related pathways.

scholarly journals Traditional Uses of Cannabinoids and New Perspectives in the Treatment of Multiple Sclerosis

Medicines ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 91 ◽  
Author(s):  
Francesca Gado ◽  
Maria Digiacomo ◽  
Marco Macchia ◽  
Simone Bertini ◽  
Clementina Manera
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Disease Progression ◽  
Endocannabinoid System ◽  
Neuroprotective Effects ◽  
Demyelinating Disorder ◽  
Immune Mediated ◽  
The Central Nervous System

Recent findings highlight the emerging role of the endocannabinoid system in the control of symptoms and disease progression in multiple sclerosis (MS). MS is a chronic, immune-mediated, demyelinating disorder of the central nervous system with no cure so far. It is widely reported in the literature that cannabinoids might be used to control MS symptoms and that they also might exert neuroprotective effects and slow down disease progression. This review aims to give an overview of the principal cannabinoids (synthetic and endogenous) used for the symptomatic amelioration of MS and their beneficial outcomes, providing new potentially possible perspectives for the treatment of this disease.

scholarly journals CD226 Gly307Ser Association With Neuromyelitis Optica in Southern Han Chinese

2012 ◽  
Vol 39 (4) ◽  
pp. 488-490 ◽  
Author(s):  
Chao Liu ◽  
Guansan Wang ◽  
Hong Liu ◽  
Yue Li ◽  
Jin Li ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Autoimmune Diseases ◽  
Neuromyelitis Optica ◽  
Han Chinese ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Relapsing Remitting Multiple Sclerosis

Background:Neuromyelitis optica (NMO) and multiple sclerosis (MS) are autoimmune diseases of the central nervous system with complex pathogeneses. NMO was once considered to be a severe variant of MS. There has been more evidence that a non-synonymous exchange (rs763361/Gly307Ser) in the gene for CD226 is linked to several autoimmune diseases including multiple sclerosis (MS). However, no studies have investigated the role of rs763361 in the pathogenesis of NMO.Objectives:The goal of our study is to evaluate the role of CD226 Gly307Ser in neuromyelitis optica (NMO) in Southern Han Chinese.Methods:Eight-nine NMO patients, 93 relapsing-remitting multiple sclerosis (RRMS) patients, and 122 controls (CTLs) were enrolled. The rs763361 alleles of the subjects were determined by sequencing-based typing.Results:The results strongly support that the TT genotypes are associated with NMO but are not significantly correlated with susceptibility for MS.Conclusions:CD226 Gly307Ser may correlate with risk of NMO in Southern Han Chinese.

scholarly journals Pericytes for Therapeutic Approaches to Ischemic Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Lu Cao ◽  
Yanbo Zhou ◽  
Mengguang Chen ◽  
Li Li ◽  
Wei Zhang
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ischemic Stroke ◽  
Therapeutic Target ◽  
Neurological Disorders ◽  
Neurovascular Unit ◽  
Therapeutic Approaches ◽  
Multipotent Cells ◽  
The Central Nervous System

Pericytes are perivascular multipotent cells located on capillaries. Although pericytes are discovered in the nineteenth century, recent studies have found that pericytes play an important role in maintaining the blood—brain barrier (BBB) and regulating the neurovascular system. In the neurovascular unit, pericytes perform their functions by coordinating the crosstalk between endothelial, glial, and neuronal cells. Dysfunction of pericytes can lead to a variety of diseases, including stroke and other neurological disorders. Recent studies have suggested that pericytes can serve as a therapeutic target in ischemic stroke. In this review, we first summarize the biology and functions of pericytes in the central nervous system. Then, we focus on the role of dysfunctional pericytes in the pathogenesis of ischemic stroke. Finally, we discuss new therapies for ischemic stroke based on targeting pericytes.

Insights into multiple sclerosis provided by non-coding RNAs: meeting summary from the symposium ‘Non-coding RNAs in autoimmune disorders of the central nervous system’ on 5 April 2013 in Warsaw, Poland

2014 ◽  
Vol 20 (11) ◽  
pp. 1439-1442 ◽  
Author(s):  
Marcin P Mycko ◽  
Howard L Weiner ◽  
Krzysztof W Selmaj
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cell Biology ◽  
Potential Role ◽  
Mechanisms Of Action ◽  
Ribonucleic Acids ◽  
The Central Nervous System ◽  
Non Coding Rnas ◽  
Autoimmune Demyelination

More than 80% of the human genome is biochemically active, whereas less than 3% of the genome encodes proteins. The emerging field of non-coding ribonucleic acids (RNAs) that are products of the genome, but do not program proteins, has revolutionized our understanding of cell biology. This was followed by a growing interest in the role of non-coding RNAs in the pathogenesis of human diseases, including multiple sclerosis (MS). In April 2013, a symposium in Warsaw, Poland, was the first meeting entirely dedicated to advances in the understanding of the roles of various subclasses of non-coding RNAs and showcased their involvement in autoimmune demyelination and MS. New mechanisms of action of small non-coding RNAs, as well as the advent of long non-coding RNAs were discussed, including the potential role of non-coding RNAs as MS biomarkers and their use for therapeutic intervention in MS.

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