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

2014 ◽  
Vol 20 (2) ◽  
pp. 135-140 ◽  
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 ◽  
Ms Pathogenesis

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.

scholarly journals Non-coding RNAs in the Pathogenesis of Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Aadil Yousuf ◽  
Abrar Qurashi
Keyword(s):  
Multiple Sclerosis ◽  
Axonal Loss ◽  
Biological Processes ◽  
Protein Coding ◽  
The Past ◽  
The Central Nervous System ◽  
Non Coding Rnas ◽  
Genetic And Environmental Factors ◽  
Ms Pathogenesis

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.

scholarly journals MicroRNAs as Novel Regulators of Neuroinflammation

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
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.

scholarly journals Viroids as a Tool to Study RNA-Directed DNA Methylation in Plants

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1187
Author(s):  
Michael Wassenegger ◽  
Athanasios Dalakouras
Keyword(s):  
Dna Methylation ◽  
Rna Interference ◽  
Gene Silencing ◽  
Plant Cells ◽  
Transcriptional Gene Silencing ◽  
Rnai Machinery ◽  
Double Stranded Rna ◽  
Post Transcriptional Gene Silencing ◽  
Cumulative Amount

Viroids are plant pathogenic, circular, non-coding, single-stranded RNAs (ssRNAs). Members of the Pospiviroidae family replicate in the nucleus of plant cells through double-stranded RNA (dsRNA) intermediates, thus triggering the host’s RNA interference (RNAi) machinery. In plants, the two RNAi pillars are Post-Transcriptional Gene Silencing (PTGS) and RNA-directed DNA Methylation (RdDM), and the latter has the potential to trigger Transcriptional Gene Silencing (TGS). Over the last three decades, the employment of viroid-based systems has immensely contributed to our understanding of both of these RNAi facets. In this review, we highlight the role of Pospiviroidae in the discovery of RdDM, expound the gradual elucidation through the years of the diverse array of RdDM’s mechanistic details and propose a revised RdDM model based on the cumulative amount of evidence from viroid and non-viroid systems.

scholarly journals Mitochondria, Oxidative Stress, cAMP Signalling and Apoptosis: A Crossroads in Lymphocytes of Multiple Sclerosis, a Possible Role of Nutraceutics

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 21
Author(s):  
Anna Signorile ◽  
Anna Ferretta ◽  
Maddalena Ruggieri ◽  
Damiano Paolicelli ◽  
Paolo Lattanzio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
T Lymphocytes ◽  
Main Role ◽  
Apoptosis Resistance ◽  
Nutraceutical Compounds ◽  
Camp Pathway ◽  
Central Nervous Systems ◽  
Genetic And Environmental Factors

Multiple sclerosis (MS) is a complex inflammatory and neurodegenerative chronic disease that involves the immune and central nervous systems (CNS). The pathogenesis involves the loss of blood–brain barrier integrity, resulting in the invasion of lymphocytes into the CNS with consequent tissue damage. The MS etiology is probably a combination of immunological, genetic, and environmental factors. It has been proposed that T lymphocytes have a main role in the onset and propagation of MS, leading to the inflammation of white matter and myelin sheath destruction. Cyclic AMP (cAMP), mitochondrial dysfunction, and oxidative stress exert a role in the alteration of T lymphocytes homeostasis and are involved in the apoptosis resistance of immune cells with the consequent development of autoimmune diseases. The defective apoptosis of autoreactive lymphocytes in patients with MS, allows these cells to perpetuate, within the CNS, a continuous cycle of inflammation. In this review, we discuss the involvement in MS of cAMP pathway, mitochondria, reactive oxygen species (ROS), apoptosis, and their interaction in the alteration of T lymphocytes homeostasis. In addition, we discuss a series of nutraceutical compounds that could influence these aspects.

scholarly journals MicroRNAs in Cardiac Autophagy: Small Molecules and Big Role

Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 104 ◽  
Author(s):  
Teng Sun ◽  
Meng-Yang Li ◽  
Pei-Feng Li ◽  
Ji-Min Cao
Keyword(s):  
Cardiac Fibrosis ◽  
Heart Diseases ◽  
Critical Role ◽  
Transcriptional Gene Silencing ◽  
Close Link ◽  
Post Transcriptional Gene Silencing ◽  
Evolutionarily Conserved ◽  
Cardiac Disorders ◽  
Cellular Components

Autophagy, which is an evolutionarily conserved process according to the lysosomal degradation of cellular components, plays a critical role in maintaining cell homeostasis. Autophagy and mitochondria autophagy (mitophagy) contribute to the preservation of cardiac homeostasis in physiological settings. However, impaired or excessive autophagy is related to a variety of diseases. Recently, a close link between autophagy and cardiac disorders, including myocardial infarction, cardiac hypertrophy, cardiomyopathy, cardiac fibrosis, and heart failure, has been demonstrated. MicroRNAs (miRNAs) are a class of small non-coding RNAs with a length of approximately 21–22 nucleotides (nt), which are distributed widely in viruses, plants, protists, and animals. They function in mediating the post-transcriptional gene silencing. A growing number of studies have demonstrated that miRNAs regulate cardiac autophagy by suppressing the expression of autophagy-related genes in a targeted manner, which are involved in the pathogenesis of heart diseases. This review summarizes the role of microRNAs in cardiac autophagy and related cardiac disorders. Furthermore, we mainly focused on the autophagy regulation pathways, which consisted of miRNAs and their targeted genes.

scholarly journals Comparative reactions of recombinant papaya ringspot viruses with chimeric coat protein (CP) genes and wild-type viruses on CP-transgenic papaya

2001 ◽  
Vol 82 (11) ◽  
pp. 2827-2836 ◽  
Author(s):  
Chu-Hui Chiang ◽  
Ju-Jung Wang ◽  
Fuh-Jyh Jan ◽  
Shyi-Dong Yeh ◽  
Dennis Gonsalves
Keyword(s):  
Coat Protein ◽  
Sequence Similarity ◽  
Transcriptional Gene Silencing ◽  
Papaya Ringspot Virus ◽  
Wild Type ◽  
Coding Region ◽  
Transgenic Papaya ◽  
Cp Gene ◽  
Post Transcriptional Gene Silencing

Transgenic papaya cultivars SunUp and Rainbow express the coat protein (CP) gene of the mild mutant of papaya ringspot virus (PRSV) HA. Both cultivars are resistant to PRSV HA and other Hawaii isolates through homology-dependent resistance via post-transcriptional gene silencing. However, Rainbow, which is hemizygous for the CP gene, is susceptible to PRSV isolates from outside Hawaii, while the CP-homozygous SunUp is resistant to most isolates but susceptible to the YK isolate from Taiwan. To investigate the role of CP sequence similarity in overcoming the resistance of Rainbow, PRSV HA recombinants with various CP segments of the YK isolate were constructed and evaluated on Rainbow, SunUp and non-transgenic papaya. Non-transgenic papaya were severely infected by all recombinants, but Rainbow plants developed a variety of symptoms. On Rainbow, a recombinant with the entire CP gene of YK caused severe symptoms, while recombinants with only partial YK CP sequences produced a range of milder symptoms. Interestingly, a recombinant with a YK segment from the 5′ region of the CP gene caused very mild, transient symptoms, whereas recombinants with YK segments from the middle and 3′ parts of the CP gene caused prominent and lasting symptoms. SunUp was resistant to all but two recombinants, which contained the entire CP gene or the central and 3′-end regions of the CP gene and the 3′ non-coding region of YK, and the resulting symptoms were mild. It is concluded that the position of the heterologous sequences in the recombinants influences their pathogenicity on Rainbow.

scholarly journals Multiple Sclerosis and Obesity: Possible Roles of Adipokines

2016 ◽  
Vol 2016 ◽  
pp. 1-24 ◽  
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 ◽  
The Central Nervous System ◽  
Ms Pathogenesis

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.

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