multiple sclerosis epigenetic

BACKGROUND: The HLA-DRB1 gene in the major histocompatibility complex (MHC) region in chromosome 6p21 is the strongest genetic factor identified as influencing multiple sclerosis (MS) susceptibility. DNA methylation changes associated with MS have been consistently detected at the MHC region. However, understanding the full scope of epigenetic regulations of the MHC remains incomplete, due in part to the limited coverage of this region by standard whole genome bisulfite sequencing or array-based methods...

Elevated levels of saturated very long-chain fatty acids (VLCFAs) in cell membranes and secreted lipoparticles have been associated with neurotoxicity and, therefore, require tight regulation. Excessive VLCFAs are imported into peroxisomes for degradation by β-oxidation. Impaired VLCFA catabolism due to primary or secondary peroxisomal alterations is featured in neurodegenerative and neuroinflammatory disorders such as X-linked adrenoleukodystrophy and multiple sclerosis (MS). Here, we identified that healthy human macrophages upregulate the peroxisomal genes involved in β-oxidation during myelin phagocytosis and pro-inflammatory activation, and that this response is impaired in peripheral macrophages and phagocytes in brain white matter lesions in MS patients...

Currently, there is a lack of effective medicines capable of halting or reversing the progression of neurodegenerative disorders, including amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, or Alzheimer's disease. Given the unmet medical need, it is necessary to reevaluate the existing paradigms of how to target these diseases. When considering neurodegenerative diseases from a systemic neurometabolic perspective, it becomes possible to explain the shared pathological features. This innovative approach presented in this paper draws upon extensive research conducted by the authors and researchers worldwide...

BACKGROUND: The etiology of Multiple sclerosis (MS) is complicated and can be affected by several environmental factors, such as Mycobacterium avium subspecies paratuberculosis (MAP) infection in genetically predisposed individuals. The link between MAP and MS depends on host genetic and epigenetic aspects and population-based features that require further investigation. We aimed to study the possible role of MAP in triggering MS using molecular and serological methods. MATERIALS AND METHODS: This case-control study examined 200 blood samples (100 MS patients and 100 HCs) to search for the MAP-specific IS900 gene...

Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS that affects millions of people worldwide. The causes of the disease remain unknown despite extensive efforts to understand it. CircRNAs are a unique class of endogenous non-coding RNA that are abundant, stable, conserved, and specifically expressed molecules, making them a promising biomarker of diseases. This review investigates the role of circRNA in MS pathogenicity and their potential as a biomarker through a comprehensive literature search conducted in 8 scientific databases...

Multiple sclerosis, a condition characterised by demyelination and axonal damage in the central nervous system, is due to autoreactive immune cells that recognise myelin antigens. Alteration of the immune balance can promote the onset of immune deficiencies, loss of immunosurveillance, and/or development of autoimmune disorders such as MS. Numerous enzymes, transcription factors, signal transducers, and membrane proteins contribute to the control of immune system activity. The "transcriptional machine" of eukaryotic cells is a complex system composed not only of mRNA but also of non-coding elements grouped together in the set of non-coding RNAs...

SnoRNAs (small non-coding RNAs) have recently gained prominence in autoimmune diseases, revealing their crucial role in modulating the immune response and contributing to disease pathogenesis. Initially known for their involvement in ribosomal RNA processing and modification, molecular biology and genomics advancements have uncovered their broader impact on cellular function, especially in autoimmune disorders. Autoimmune diseases represent conditions characterized by the immune system's erroneous attacks on self-tissues, encompassing disorders like systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis...

Multiple sclerosis (MS) is a primary inflammatory demyelinating disease with different clinical courses and subtypes. The present study aimed to determine whether mitochondrial dysfunction and sirtuins 1 and 3, as metabolism and epigenetic modifying factors, might contribute to MS disease progression measured by physical disability and cognitive impairment.The volunteers (n = 20 controls, n = 59 MS) were recruited and assessed for cognitive function and disability scores; then, patients were clinically classified as relapsing-remitting (RR) in remission phase, RR in relapse phase, and secondary progressive MS...

The relationships between motor neurons and the skeletal muscle during development and in pathologic contexts are addressed in this Chapter.We discuss the developmental interplay of muscle and nervous tissue, through neurotrophins and the activation of differentiation and survival pathways. After a brief overview on muscular regulatory factors, we focus on the contribution of muscle to early and late neurodevelopment. Such a role seems especially intriguing in relation to the epigenetic shaping of developing motor neuron fate choices...

BACKGROUND: In 2005, we reported 3 patients with bilateral optic nerve damage early in life. These patients had stable vision for decades but then experienced significant bilateral vision loss with no obvious cause. Our hypothesis, novel at that time, was that the late decline of vision was due to age-related attrition of retinal ganglion cells superimposed on a reduced neuronal population due to the earlier injury. EVIDENCE ACQUISITION: The field of epigenetics provides a new paradigm with which to consider the normal aging process and the impact of neuronal injury, which has been shown to accelerate aging...

In multiple sclerosis (MS), the invasion of the central nervous system by peripheral immune cells is followed by the activation of resident microglia and astrocytes. This cascade of events results in demyelination, which triggers neuronal damage and death. The molecular signals in neurons responsible for this damage are not yet fully characterized. In MS, retinal ganglion cell neurons (RGCs) of the central nervous system (CNS) undergo axonal injury and cell death. This phenomenon is mirrored in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS...

Multiple sclerosis (MS) is a debilitating autoimmune condition caused by demyelination, neurodegeneration and persistent inflammation of the central nervous system. Pediatric multiple sclerosis (PMS) is a relatively rare form of the disease that affects a significant number of individuals with MS. Environmental exposures, such as viral infections and smoking, can interact with MS-associated human leukocyte antigens (HLA) risk alleles and influence the immune response. Upregulation of immune response results in the disruption of immune balance leading to cascade of inflammatory events...

Environmental triggers often work via signal transduction cascades that modulate the epigenome and transcriptome of cell types involved in the disease process. Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system being characterized by a combination of recurring inflammation, demyelination and progressive loss of axons. The mechanisms of MS onset are not fully understood and genetic variants may explain only some 20% of the disease susceptibility. From the environmental factors being involved in disease development low vitamin D levels have been shown to significantly contribute to MS susceptibility...

Temporomandibular joint osteoarthritis (TMJOA) is a kind of degenerative lesion in temporomandibular joint disorders. The pathogenesis of TMJOA is complex. Among them, excessive mechanical stress plays an important role, which can cause a series of pathological changes, including synovial inflammation, chondrocyte death, osteogenic and adipogenic differentiation, degradation of extracellular matrix of cartilage, angiogenesis, osteochondral interface sclerosis, subchondral bone remodeling, degeneration of articular discs, etc...

Poly (ADP-ribose) polymerase-1 (PARP-1) is the most extensively studied member of the PARP superfamily, with its primary function being the facilitation of DNA damage repair processes. Parthanatos is a type of regulated cell death cascade initiated by PARP-1 hyperactivation, which involves multiple subroutines, including the accumulation of ADP-ribose polymers (PAR), binding of PAR and apoptosis-inducing factor (AIF), release of AIF from the mitochondria, the translocation of the AIF/macrophage migration inhibitory factor (MIF) complex, and massive MIF-mediated DNA fragmentation...

Understanding the molecular mechanisms underlying neuro-urological disorders is crucial for the development of targeted therapeutic interventions. Through the establishment of comprehensive biobanks, researchers can collect and store various biological specimens, including urine, blood, tissue, and DNA samples, to study these mechanisms. In the context of neuro-urology, biobanking facilitates the identification of genetic variations, epigenetic modifications, and gene expression patterns associated with neurogenic lower urinary tract dysfunction...

Multiple sclerosis is a chronic demyelinating disorder with an unclear etiology. A key role is thought to be played by Th17 cells and microRNAs associated with Th17, such as miR-155, miR-326 and miR-223. The present study compared the methylation and hydroxymethylation levels of CpG sites within promoters of these microRNA between MS patients and controls using PBMCs and analyzed their relationship with microRNA expression. Significant intergroup differences were found between the levels of 5-hmC within the CpG-1 miR-155 promoter and CpG within the miR-326 promoter; in addition, miR-155-5p and miR-223-3p expression was elevated in MS patients...

Multiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system, which is characterized by significant clinical heterogeneity. Primary progressive MS (PPMS) develops in 10-15% of patients. Unlike the most common relapsing-remitting form of MS, PPMS involves steady progress of neurodegeneration and, as a consequence, a persistent gradual increase in neurological symptoms. The peculiarities of epigenetic regulation of gene expression may be one of the reasons for the differences in the pathogenesis of the two MS forms...

Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information, with its application to neuroscience termed neuroinformatics. Data mining of omics datasets has enabled the generation of new hypotheses based on differentially regulated biological molecules associated with disease mechanisms, which can be tested experimentally for improved diagnostic and therapeutic targeting of neurodegenerative diseases. Importantly, integrating multi-omics data using a systems bioinformatics approach will advance the understanding of the layered and interactive network of biological regulation that exchanges systemic knowledge to facilitate the development of a comprehensive human brain profile...

BACKGROUND: A compelling body of evidence implicates cigarette smoking and lung inflammation in Multiple Sclerosis (MS) susceptibility and progression. Previous studies have reported epigenetic age (DNAm age) acceleration in blood immune cells and in glial cells of people with MS (pwMS) compared to healthy controls (HC). OBJECTIVES: We aimed to examine biological ageing in lung immune cells in the context of MS and smoking. METHODS: We analyzed age acceleration residuals in lung bronchoalveolar lavage (BAL) cells, constituted of mainly alveolar macrophages, from 17 pwMS and 22 HC in relation to smoking using eight DNA methylation-based clocks, namely AltumAge, Horvath, GrimAge, PhenoAge, Zhang, SkinBlood, Hannum, Monocyte clock as well as two RNA-based clocks, which capture different aspects of biological ageing...