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multiple sclerosis epigenetic

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https://www.readbyqxmd.com/read/28915632/decitabine-inhibits-t-cell-proliferation-via-a-novel-tet2-dependent-mechanism-and-exerts-potent-protective-effect-in-mouse-auto-and-allo-immunity-models
#1
Xue Wang, Jun Wang, Yong Yu, Tonghui Ma, Ping Chen, Bing Zhou, Ran Tao
Multiple sclerosis (MS) is an autoimmune disease characterized by the dysregulated immune response including innate and adaptive immune responses. Increasing evidence has proven the importance of epigenetic modification in the progression of MS. Recent studies revealed that low-dose decitabine (Dec, 5-Aza-2'-deoxycytidine), which incorporates into replicating DNA and inhibits DNA methylation, could prevent experimental autoimmune encephalomyelitis (EAE) development by increasing the number of regulatory T cells (Tregs)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28843454/pediatric-multiple-sclerosis-genes-environment-and-a-comprehensive-therapeutic-approach
#2
REVIEW
Ryan Cappa, Liana Theroux, J Nicholas Brenton
BACKGROUND: Pediatric multiple sclerosis is an increasingly recognized and studied disorder that accounts for 3% to 10% of all patients with multiple sclerosis. The risk for pediatric multiple sclerosis is thought to reflect a complex interplay between environmental and genetic risk factors. MAIN FINDINGS: Environmental exposures, including sunlight (ultraviolet radiation, vitamin D levels), infections (Epstein-Barr virus), passive smoking, and obesity, have been identified as potential risk factors in youth...
October 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28829212/targeting-methionine-cycle-as-a-potential-therapeutic-strategy-for-immune-disorders
#3
Heng Li, Huimin Lu, Wei Tang, Jianping Zuo
Methionine cycle plays an essential role in regulating many cellular events, especially transmethylation reactions, incorporating the methyl donor S-adenosylmethionine (SAM). The transmethylations and substances involved in the cycle have shown complicated effects and mechanisms on immunocytes developments and activations, and exert crucial impacts on the pathological processes in immune disorders. Areas covered: Methionine cycle has been considered as an effective means of drug developments. This review discussed the role of methionine cycle in immune responses and summarized the potential therapeutic strategies based on the cycle, including SAM analogs, methyltransferase inhibitors, S-adenosylhomocysteine hydrolase (SAHH) inhibitors, adenosine receptors specific agonists or antagonists and homocysteine (Hcy)-lowering reagents, in treating human immunodeficiency virus (HIV) infections, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), systemic sclerosis (SSc) and other immune disorders...
August 22, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28821749/dna-methylation-in-demyelinated-multiple-sclerosis-hippocampus
#4
Anthony M Chomyk, Christina Volsko, Ajai Tripathi, Sadie A Deckard, Bruce D Trapp, Robert J Fox, Ranjan Dutta
Multiple Sclerosis (MS) is an immune-mediated demyelinating disease of the human central nervous system (CNS). Memory impairments and hippocampal demyelination are common features in MS patients. Our previous data have shown that demyelination alters neuronal gene expression in the hippocampus. DNA methylation is a common epigenetic modifier of gene expression. In this study, we investigated whether DNA methylation is altered in MS hippocampus following demyelination. Our results show that mRNA levels of DNA methyltransferase were increased in demyelinated MS hippocampus, while de-methylation enzymes were decreased...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808113/lncrna-gas5-inhibits-microglial-m2-polarization-and-exacerbates-demyelination
#5
Dingya Sun, Zhongwang Yu, Xue Fang, Mingdong Liu, Yingyan Pu, Qi Shao, Dan Wang, Xiaolin Zhao, Aijun Huang, Zhenghua Xiang, Chao Zhao, Robin Jm Franklin, Li Cao, Cheng He
The regulation of inflammation is pivotal for preventing the development or reoccurrence of multiple sclerosis (MS). A biased ratio of high-M1 versus low-M2 polarized microglia is a major pathological feature of MS Here, using microarray screening, we identify the long noncoding RNA (lncRNA) GAS5 as an epigenetic regulator of microglial polarization. Gain- and loss-of-function studies reveal that GAS5 suppresses microglial M2 polarization. Interference with GAS5 in transplanted microglia attenuates the progression of experimental autoimmune encephalomyelitis (EAE) and promotes remyelination in a lysolecithin-induced demyelination model...
August 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28797086/epigenetic-differences-between-monozygotic-twins-discordant-for-amyotrophic-lateral-sclerosis-als-provide-clues-to-disease-pathogenesis
#6
Paul E Young, Stephen Kum Jew, Michael E Buckland, Roger Pamphlett, Catherine M Suter
Amyotrophic lateral sclerosis (ALS) is a devastating late-onset neurodegenerative disorder in which only a small proportion of patients carry an identifiable causative genetic lesion. Despite high heritability estimates, a genetic etiology for most sporadic ALS remains elusive. Here we report the epigenetic profiling of five monozygotic twin pairs discordant for ALS, four with classic ALS and one with the progressive muscular atrophy ALS variant, in whom previous whole genome sequencing failed to uncover a genetic basis for their disease discordance...
2017: PloS One
https://www.readbyqxmd.com/read/28766461/hypermethylation-of-mir21-in-cd4-t-cells-from-patients-with-relapsing-remitting-multiple-sclerosis-associates-with-lower-mirna-21-levels-and-concomitant-up-regulation-of-its-target-genes
#7
Sabrina Ruhrmann, Ewoud Ewing, Eliane Piket, Lara Kular, Julio Cesar Cetrulo Lorenzi, Sunjay Jude Fernandes, Hiromasa Morikawa, Shahin Aeinehband, Sergi Sayols-Baixeras, Stella Aslibekyan, Devin M Absher, Donna K Arnett, Jesper Tegner, David Gomez-Cabrero, Fredrik Piehl, Maja Jagodic
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic and environmental risk factors. OBJECTIVE: We sought to identify DNA methylation changes in CD4+ T cells in patients with relapsing-remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls (HC)...
August 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28754822/epigenetic-research-in-multiple-sclerosis-progress-challenges-and-opportunities
#8
Galina Zheleznyakova, Eliane Piket, Francesco Marabita, Majid Pahlevan Kakhki, Ewoud Ewing, Sabrina Ruhrmann, Maria Needhamsen, Maja Jagodic, Lara Kular
Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. MS likely results from a complex interplay between predisposing causal gene variants (the strongest influence coming from HLA class II locus) and environmental risk factors such as smoking, infectious mononucleosis and lack of sun exposure/vitamin D. However, little is known about the mechanisms underlying MS development and progression. Moreover, the clinical heterogeneity and variable response to treatment represent additional challenges to a comprehensive understanding and efficient treatment of disease...
July 28, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28739526/chronic-mild-stress-exacerbates-severity-of-experimental-autoimmune-encephalomyelitis-in-association-with-altered-non-coding-rna-and-metabolic-biomarkers
#9
Brietta Gerrard, Vaibhav Singh, Olena Babenko, Isabelle Gauthier, V Wee Yong, Igor Kovalchuk, Artur Luczak, Gerlinde A S Metz
The causal factors determining the onset and severity of multiple sclerosis (MS) are not well understood. Here, we investigated the influence of chronic stress on clinical symptoms, metabolic and epigenetic manifestations of experimental autoimmune encephalomyelitis (EAE), a common animal model of MS. Lewis rats were immunized for monophasic EAE with MBP69-88 and were exposed to chronic stress for 37days starting 7days prior to immunization. The exposure to stress accelerated and exacerbated the clinical symptoms of EAE...
July 21, 2017: Neuroscience
https://www.readbyqxmd.com/read/28736194/the-epigenetic-drug-trichostatin-a-ameliorates-experimental-autoimmune-encephalomyelitis-via-t-cell-tolerance-induction-and-impaired-influx-of-t-cells-into-the-spinal-cord
#10
Arathi Jayaraman, Advait Soni, Bellur S Prabhakar, Mark Holterman, Sundararajan Jayaraman
Multiple sclerosis is a T cell mediated chronic demyelinating disease of the central nervous system. Although currently available therapies reduce relapses, they do not facilitate tolerization of myelin antigen-specific T lymphocytes to ensure prolonged protection against multiple sclerosis. Here, we show that treatment of NOD mice with the histone deacetylase inhibitor, Trichostatin A affords robust protection against myelin peptide induced experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis...
July 20, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28729889/differential-methylation-at-mhc-in-cd4-t-cells-is-associated-with-multiple-sclerosis-independently-of-hla-drb1
#11
Vicki E Maltby, Rodney A Lea, Katherine A Sanders, Nicole White, Miles C Benton, Rodney J Scott, Jeannette Lechner-Scott
BACKGROUND: Although many genetic variants have been associated with multiple sclerosis (MS) risk, they do not explain all the disease risk and there remains uncertainty as to how these variants contribute to disease. DNA methylation is an epigenetic mechanism that can influence gene expression and has the potential to mediate the effects of environmental factors on MS. In a previous study, we found a differentially methylation region (DMR) at MHC HLA-DRB1 that was associated within relapsing-remitting MS (RRMS) patients in CD4(+) T cells...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28713244/regulatory-roles-of-long-non-coding-rnas-in-the-central-nervous-system-and-associated-neurodegenerative-diseases
#12
REVIEW
Zhenzhen Quan, Da Zheng, Hong Qing
Accumulating studies have revealed that the human genome encodes tens of thousands of long non-coding RNAs (lncRNAs), which participate in multiple biological networks modulating gene expression via transcriptional, post-transcriptional and epigenetic regulation. Strikingly, a large fraction of tissue-specific lncRNAs are expressed in the Central Nervous System (CNS) with precisely regulated temporal and spatial expression patterns. These brain-specific lncRNAs are also featured with the cell-type specificity, the highest signals of evolutionary conservation, and their preferential location adjacent to brain-expressed protein-coding genes...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28707075/line-1-hypermethylation-in-serum-cell-free-dna-of-relapsing-remitting-multiple-sclerosis-patients
#13
Marina Dunaeva, Merel Derksen, Ger J M Pruijn
Concentrations of cell-free DNA (cfDNA) circulating in blood and its epigenetic variation, such as DNA methylation, may provide useful diagnostic or prognostic information. Long interspersed nuclear element-1 (LINE-1) constitutes approximately 20% of the human genome and its 5'UTR region is CpG rich. Due to its wide distribution, the methylation level of the 5'UTR of LINE-1 can serve as a surrogate marker of global genomic DNA methylation. The aim of the current study was to investigate whether the methylation status of LINE-1 elements in serum cell-free DNA differs between relapsing remitting multiple sclerosis (RRMS) patients and healthy control subjects (CTR)...
July 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28606110/a-c9orf72-bac-mouse-model-recapitulates-key-epigenetic-perturbations-of-als-ftd
#14
Rustam Esanov, Gabriela Toro Cabrera, Nadja S Andrade, Tania F Gendron, Robert H Brown, Michael Benatar, Claes Wahlestedt, Christian Mueller, Zane Zeier
BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal and progressive neurodegenerative disorder with identified genetic causes representing a significant minority of all cases. A GGGGCC hexanucleotide repeat expansion (HRE) mutation within the C9ORF72 gene has recently been identified as the most frequent known cause of ALS. The expansion leads to partial heterochromatinization of the locus, yet mutant RNAs and dipeptide repeat proteins (DPRs) are still produced in sufficient quantities to confer neurotoxicity...
June 12, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28599286/decitabine-inhibits-t-cell-proliferation-via-a-novel-tet2-dependent-mechanism-and-exerts-potent-protective-effect-in-mouse-auto-and-allo-immunity-models
#15
Xue Wang, Jun Wang, Yong Yu, Tonghui Ma, Ping Chen, Bing Zhou, Ran Tao
Multiple sclerosis (MS) is an autoimmune disease characterized by the dysregulated immune response including innate and adaptive immune responses. Increasing evidence has proven the importance of epigenetic modification in the progression of MS. Recent studies revealed that low-dose decitabine (Dec, 5-Aza-2'-deoxycytidine), which incorporates into replicating DNA and inhibits DNA methylation, could prevent experimental autoimmune encephalomyelitis (EAE) development by increasing the number of regulatory T cells (Tregs)...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28516431/a-comparison-of-neuroimaging-abnormalities-in-multiple-sclerosis-major-depression-and-chronic-fatigue-syndrome-myalgic-encephalomyelitis-is-there-a-common-cause
#16
REVIEW
Gerwyn Morris, Michael Berk, Basant K Puri
There is copious evidence of abnormalities in resting-state functional network connectivity states, grey and white matter pathology and impaired cerebral perfusion in patients afforded a diagnosis of multiple sclerosis, major depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis). Systemic inflammation may well be a major element explaining such findings. Inter-patient and inter-illness variations in neuroimaging findings may arise at least in part from regional genetic, epigenetic and environmental variations in the functions of microglia and astrocytes...
May 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28486971/a-role-for-cathepsin-z-in-neuroinflammation-provides-mechanistic-support-for-an-epigenetic-risk-factor-in-multiple-sclerosis
#17
Euan R O Allan, Rhiannon I Campden, Benjamin W Ewanchuk, Pankaj Tailor, Dale R Balce, Neil T McKenna, Catherine J Greene, Amy L Warren, Thomas Reinheckel, Robin M Yates
BACKGROUND: Hypomethylation of the cathepsin Z locus has been proposed as an epigenetic risk factor for multiple sclerosis (MS). Cathepsin Z is a unique lysosomal cysteine cathepsin expressed primarily by antigen presenting cells. While cathepsin Z expression has been associated with neuroinflammatory disorders, a role for cathepsin Z in mediating neuroinflammation has not been previously established. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in both wildtype mice and mice deficient in cathepsin Z...
May 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28412046/the-epigenetic-mechanism-for-discordance-of-autoimmunity-in-monozygotic-twins
#18
REVIEW
Zhongyuan Xiang, Yuanqing Yang, Christopher Chang, Qianjin Lu
Monozygotic twins share an identical DNA sequence but are not truly "identical". In fact, when it comes to health and disease, they may often display some level of phenotypic discordance. The cause of this discordance is often unknown. Epigenetic modifications such as DNA methylation, histone modification, and microRNAs-mediated regulation regulate gene expression and are sensitive to external stimuli. These modifications may be seen to bridge the gap between genetics and the environment. Over the years, the importance of epigenetics as a primary mechanism for the role that the environment plays in defining phenotype has been increasingly appreciated...
April 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28386263/adaptive-immunity-is-the-key-to-the-understanding-of-autoimmune-and-paraneoplastic-inflammatory-central-nervous-system-disorders
#19
REVIEW
Robert Weissert
There are common aspects and mechanisms between different types of autoimmune diseases such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), and autoimmune encephalitis (AE) as well as paraneoplastic inflammatory disorders of the central nervous system. To our present knowledge, depending on the disease, T and B cells as well as antibodies contribute to various aspects of the pathogenesis. Possibly the events leading to the breaking of tolerance between the different diseases are of great similarity and so far, only partially understood...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28362657/epigenetics-of-cd4-t-cells-in-autoimmune-diseases
#20
Zijun Wang, Christopher Chang, Qianjin Lu
PURPOSE OF REVIEW: Autoimmune disorders are a group of overactive symptoms because of abnormal immune responses. Progress of novel mechanisms for autoimmune diseases has been restrained by incomplete understanding of immune disturbance. Recent advances in autoimmune diseases have been well documented by epigenetic alterations (DNA methylation, histone modification, and microRNAs), which alter the transcription activity of genes that are involved in autoimmune responses. RECENT FINDINGS: Multiple environmental factors (trichloroethylene, breast milk, and vitamin C) initiate aberrant epigenetic modifications in CD4 T cells, leading to a list of transcriptional deregulations in several genes (Ifng, Cd70, Tnf, Dnmt3a, and Foxp3) that determine T-cell identity...
July 2017: Current Opinion in Rheumatology
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