Non-coding RNAs in the Pathogenesis of Multiple Sclerosis

Non Coding Rnas ◽

Genetic And Environmental Factors ◽

Multiple sclerosis (MS) is an early onset chronic neurological condition in adults characterized by inflammation, demyelination, gliosis, and axonal loss in the central nervous system. The pathological cause of MS is complex and includes both genetic and environmental factors. Non-protein-coding RNAs (ncRNAs), specifically miRNAs and lncRNAs, are important regulators of various biological processes. Over the past decade, many studies have investigated both miRNAs and lncRNAs in patients with MS. Since then, insightful knowledge has been gained in this field. Here, we review the role of miRNAs and lncRNAs in MS pathogenesis and discuss their implications for diagnosis and treatment.

Multiple Sclerosis and Obesity: Possible Roles of Adipokines

Mediators of Inflammation ◽

10.1155/2016/4036232 ◽

2016 ◽

Vol 2016 ◽

pp. 1-24 ◽

Cited By ~ 36

Author(s):

José de Jesús Guerrero-García ◽

Lucrecia Carrera-Quintanar ◽

Rocío Ivette López-Roa ◽

Ana Laura Márquez-Aguirre ◽

Argelia Esperanza Rojas-Mayorquín ◽

...

Keyword(s):

Multiple Sclerosis ◽

Early Life ◽

Neural Tissue ◽

Autoimmune Disorder ◽

Susceptibility Factor ◽

Related Risk ◽

Inflammatory State ◽

Multiple Sclerosis (MS) is an autoimmune disorder of the Central Nervous System that has been associated with several environmental factors, such as diet and obesity. The possible link between MS and obesity has become more interesting in recent years since the discovery of the remarkable properties of adipose tissue. Once MS is initiated, obesity can contribute to increased disease severity by negatively influencing disease progress and treatment response, but, also, obesity in early life is highly relevant as a susceptibility factor and causally related risk for late MS development. The aim of this review was to discuss recent evidence about the link between obesity, as a chronic inflammatory state, and the pathogenesis of MS as a chronic autoimmune and inflammatory disease. First, we describe the main cells involved in MS pathogenesis, both from neural tissue and from the immune system, and including a new participant, the adipocyte, focusing on their roles in MS. Second, we concentrate on the role of several adipokines that are able to participate in the mediation of the immune response in MS and on the possible cross talk between the latter. Finally, we explore recent therapy that involves the transplantation of adipocyte precursor cells for the treatment of MS.

Long Non-Coding RNAs and Related Molecular Pathways in the Pathogenesis of Epilepsy

International Journal of Molecular Sciences ◽

10.3390/ijms20194898 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4898 ◽

Cited By ~ 5

Author(s):

Villa ◽

Lavitrano ◽

Combi

Keyword(s):

Biological Processes ◽

Complete Understanding ◽

Aberrant Expression ◽

Protein Coding ◽

Diagnostic Biomarkers ◽

Functional Roles ◽

Non Coding Rnas ◽

Underlying Mechanisms ◽

Coding Capacity

Epilepsy represents one of the most common neurological disorders characterized by abnormal electrical activity in the central nervous system (CNS). Recurrent seizures are the cardinal clinical manifestation. Although it has been reported that the underlying pathological processes include inflammation, changes in synaptic strength, apoptosis, and ion channels dysfunction, currently the pathogenesis of epilepsy is not yet completely understood. Long non-coding RNAs (lncRNAs), a class of long transcripts without protein-coding capacity, have emerged as regulatory molecules that are involved in a wide variety of biological processes. A growing number of studies reported that lncRNAs participate in the regulation of pathological processes of epilepsy and they are dysregulated during epileptogenesis. Moreover, an aberrant expression of lncRNAs linked to epilepsy has been observed both in patients and in animal models. In this review, we summarize latest advances concerning the mechanisms of action and the involvement of the most dysregulated lncRNAs in epilepsy. However, the functional roles of lncRNAs in the disease pathogenesis are still to be explored and we are only at the beginning. Additional studies are needed for the complete understanding of the underlying mechanisms and they would result in the use of lncRNAs as diagnostic biomarkers and novel therapeutic targets.

The potential role of epigenetic modifications in the heritability of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458514520911 ◽

2014 ◽

Vol 20 (2) ◽

pp. 135-140 ◽

Cited By ~ 20

Author(s):

Yuan Zhou ◽

Steve Simpson ◽

Adele F Holloway ◽

Jac Charlesworth ◽

Ingrid van der Mei ◽

...

Keyword(s):

Multiple Sclerosis ◽

Potential Role ◽

Transcriptional Gene Silencing ◽

Epigenetic Changes ◽

Missing Heritability ◽

Significant Component ◽

Post Transcriptional Gene Silencing ◽

Genetic And Environmental Factors ◽

It is now well established that both genetic and environmental factors contribute to and interact in the development of multiple sclerosis (MS). However, the currently described causal genetic variants do not explain the majority of the heritability of MS, resulting in ‘missing heritability’. Epigenetic mechanisms, which principally include DNA methylation, histone modifications and microRNA-mediated post-transcriptional gene silencing, may contribute a significant component of this missing heritability. As the development of MS is a dynamic process potentially starting with inflammation, then demyelination, remyelination and neurodegeneration, we have reviewed the dynamic epigenetic changes in these aspects of MS pathogenesis and describe how environmental risk factors may interact with epigenetic changes to manifest in disease.

MicroRNAs as Novel Regulators of Neuroinflammation

Mediators of Inflammation ◽

10.1155/2013/172351 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 31

Author(s):

Dominika Justyna Ksiazek-Winiarek ◽

Magdalena Justyna Kacperska ◽

Andrzej Glabinski

Keyword(s):

Multiple Sclerosis ◽

Current Knowledge ◽

Neurological Diseases ◽

Small Noncoding Rnas ◽

Cellular Processes ◽

Proliferation And Apoptosis ◽

Genetic And Environmental Factors ◽

Ms Pathogenesis ◽

Fine Tune

MicroRNAs are relatively recently discovered class of small noncoding RNAs, which function as important regulators of gene expression. They fine-tune protein expression either by translational inhibition or mRNA degradation. MicroRNAs act as regulators of diverse cellular processes, such as cell differentiation, proliferation, and apoptosis. Their defective biogenesis or function has been identified in various pathological conditions, like inflammation, neurodegeneration, or autoimmunity. Multiple sclerosis is one of the predominated debilitating neurological diseases affecting mainly young adults. It is a multifactorial disorder of as yet unknown aetiology. As far, it is suggested that interplay between genetic and environmental factors is responsible for MS pathogenesis. The role of microRNAs in this pathology is now extensively studied. Here, we want to review the current knowledge of microRNAs role in multiple sclerosis.

Role of gene polymorphisms in vitamin D metabolism and in multiple sclerosis

Archives of Industrial Hygiene and Toxicology ◽

10.2478/aiht-2018-69-3065 ◽

2018 ◽

Vol 69 (1) ◽

pp. 25-31 ◽

Cited By ~ 4

Author(s):

Aylin Elkama ◽

Bensu Karahalil

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Environmental Factors ◽

Gene Polymorphisms ◽

Neurological Impairment ◽

Vitamin D Metabolism ◽

Vitamin D Levels ◽

Genetic And Environmental Factors

Abstract Multiple sclerosis (MS) is a complex inflammatory disease of the central nervous system (CNS) resulting in neurological impairment and disability. There is evidence that adequate vitamin D levels may lower the risk of MS development. The aetiology of MS is complex and involves both genetic and environmental factors. In fact, not one but several genes are believed to lead to the disease. As for environmental factors, one of the most important risk factors is vitamin D deficiency, which, in turn, is closely related to gene polymorphisms that play a role in vitamin D metabolism and regulation. However, information about these gene polymorphisms is quite contradictory. The aim of this review is to discuss the association between some of the vitamin D-related gene variants and MS.

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

Multiple Sclerosis Journal ◽

10.1177/1352458514521518 ◽

2014 ◽

Vol 20 (11) ◽

pp. 1439-1442 ◽

Cited By ~ 1

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 ◽

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.

Non-Coding RNAs in Glioma

Cancers ◽

10.3390/cancers11010017 ◽

2018 ◽

Vol 11 (1) ◽

pp. 17 ◽

Cited By ~ 31

Author(s):

Ryte Rynkeviciene ◽

Julija Simiene ◽

Egle Strainiene ◽

Vaidotas Stankevicius ◽

Jurgita Usinskiene ◽

...

Keyword(s):

Phenotypic Diversity ◽

High Grade Glioma ◽

Biological Processes ◽

Glioma Tissue ◽

Tissue Samples ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Long Non Coding Rna

Glioma is the most aggressive brain tumor of the central nervous system. The ability of glioma cells to migrate, rapidly diffuse and invade normal adjacent tissue, their sustained proliferation, and heterogeneity contribute to an overall survival of approximately 15 months for most patients with high grade glioma. Numerous studies indicate that non-coding RNA species have critical functions across biological processes that regulate glioma initiation and progression. Recently, new data emerged, which shows that the cross-regulation between long non-coding RNAs and small non-coding RNAs contribute to phenotypic diversity of glioblastoma subclasses. In this paper, we review data of long non-coding RNA expression, which was evaluated in human glioma tissue samples during a five-year period. Thus, this review summarizes the following: (I) the role of non-coding RNAs in glioblastoma pathogenesis, (II) the potential application of non-coding RNA species in glioma-grading, (III) crosstalk between lncRNAs and miRNAs (IV) future perspectives of non-coding RNAs as biomarkers for glioma.

Role of Pseudogenes in Tumorigenesis

Cancers ◽

10.3390/cancers10080256 ◽

2018 ◽

Vol 10 (8) ◽

pp. 256 ◽

Cited By ~ 29

Author(s):

Xinling Hu ◽

Liu Yang ◽

Yin-Yuan Mo

Keyword(s):

Critical Role ◽

Cellular Functions ◽

Protein Coding ◽

Master Regulators ◽

Protein Coding Genes ◽

The Past ◽

High Sequence Homology ◽

Regulation Mechanisms ◽

Non Coding Rnas

Functional genomics has provided evidence that the human genome transcribes a large number of non-coding genes in addition to protein-coding genes, including microRNAs and long non-coding RNAs (lncRNAs). Among the group of lncRNAs are pseudogenes that have not been paid attention in the past, compared to other members of lncRNAs. However, increasing evidence points the important role of pseudogenes in diverse cellular functions, and dysregulation of pseudogenes are often associated with various human diseases including cancer. Like other types of lncRNAs, pseudogenes can also function as master regulators for gene expression and thus, they can play a critical role in various aspects of tumorigenesis. In this review we discuss the latest developments in pseudogene research, focusing on how pseudogenes impact tumorigenesis through different gene regulation mechanisms. Given the high sequence homology with the corresponding parent genes, we also discuss challenges for pseudogene research.

Advances in brain imaging in multiple sclerosis

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286419859722 ◽

2019 ◽

Vol 12 ◽

pp. 175628641985972 ◽

Cited By ~ 10

Author(s):

Rosa Cortese ◽

Sara Collorone ◽

Olga Ciccarelli ◽

Ahmed T. Toosy

Keyword(s):

Multiple Sclerosis ◽

Brain Imaging ◽

Imaging Techniques ◽

Relapsing Remitting ◽

Disability Outcome ◽

Magnetic Resonance Imaging Mri ◽

Brain imaging is increasingly used to support clinicians in diagnosing multiple sclerosis (MS) and monitoring its progression. However, the role of magnetic resonance imaging (MRI) in MS goes far beyond its clinical application. Indeed, advanced imaging techniques have helped to detect different components of MS pathogenesis in vivo, which is now considered a heterogeneous process characterized by widespread damage of the central nervous system, rather than multifocal demyelination of white matter. Recently, MRI biomarkers more sensitive to disease activity than clinical disability outcome measures, have been used to monitor response to anti-inflammatory agents in patients with relapsing–remitting MS. Similarly, MRI markers of neurodegeneration exhibit the potential as primary and secondary outcomes in clinical trials for progressive phenotypes. This review will summarize recent advances in brain neuroimaging in MS from the research setting to clinical applications.

miRNAs in Microglia: Important Players in Multiple Sclerosis Pathology

ASN NEURO ◽

10.1177/1759091420981182 ◽

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 ◽

And Function ◽

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.