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multiple sclerosis epigenetic

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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
#1
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
#2
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
#3
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
#4
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
#5
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...
March 30, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28355272/vitamin-d-receptor-gene-is-epigenetically-altered-and-transcriptionally-up-regulated-in-multiple-sclerosis
#6
Teresa Ayuso, Patricia Aznar, Luis Soriano, Ander Olaskoaga, Miren Roldán, María Otano, Iratxe Ajuria, Gerardo Soriano, Francisco Lacruz, Maite Mendioroz
OBJECTIVE: Vitamin D deficiency has been linked to increased risk of multiple sclerosis (MS) and poor outcome. However, the specific role that vitamin D plays in MS still remains unknown. In order to identify potential mechanisms underlying vitamin D effects in MS, we profiled epigenetic changes in vitamin D receptor (VDR) gene to identify genomic regulatory elements relevant to MS pathogenesis. METHODS: Human T cells derived from whole blood by negative selection were isolated in a set of 23 relapsing-remitting MS (RRMS) patients and 12 controls matched by age and gender...
2017: PloS One
https://www.readbyqxmd.com/read/28320131/epigenetic-and-gene-expression-alterations-of-foxp3-in-the-t-cells-of-eae-mouse-model-of-multiple-sclerosis
#7
Ali Noori-Zadeh, Seyed Alireza Mesbah-Namin, Ali Akbar Saboor-Yaraghi
Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination and neurodegeneration of the central nervous system. It has been shown that the regulatory T (Treg) cells are responsible for maintaining tolerance to self-antigens and can suppress the autoimmune process in several animal models such as experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Recent basic studies have demonstrated that forkhead box P (FOXP3) and BTB domain and CNC homolog 2 (BACH2) are the master transcription factors of these cells playing a pivotal role in the polarization of naïve T cells into Treg cells...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28270189/characterization-of-the-hla-dr%C3%AE-1-third-hypervariable-region-amino-acid-sequence-according-to-charge-and-parental-inheritance-in-systemic-sclerosis
#8
Coline A Gentil, Hilary S Gammill, Christine T Luu, Maureen D Mayes, Dan E Furst, J Lee Nelson
BACKGROUND: Specific HLA class II alleles are associated with systemic sclerosis (SSc) risk, clinical characteristics, and autoantibodies. HLA nomenclature initially developed with antibodies as typing reagents defining DRB1 allele groups. However, alleles from different DRB1 allele groups encode the same third hypervariable region (3rd HVR) sequence, the primary T-cell recognition site, and 3rd HVR charge differences can affect interactions with T cells. We considered 3rd HVR sequences (amino acids 67-74) irrespective of the allele group and analyzed parental inheritance considered according to the 3rd HVR charge, comparing SSc patients with controls...
March 7, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28263097/transcriptional-and-epigenetic-regulation-of-follicular-t-helper-cells-and-their-role-in-autoimmunity
#9
Hong Qiu, Haijing Wu, Vera Chan, Chak-Sing Lau, Qianjin Lu
T-follicular helper (Tfh) cells are a specialized subset of T cells that provide help to B cells and promote the formation of germinal centers (GCs). Tfh cells transmit important signals to B cells that drive class switch recombination, somatic hyper-mutation, the generation of high-affinity antibodies, immunological memory and their differentiation into plasma cells or memory B cells in the GCs. Tfh-cell differentiation is regulated by the coordinated functions of distinct cytokines, including interleukin (IL)-6, IL-21, IL-12, IL-23, IL-2, IL-7 and transforming growth factor-β (TGF-β), as well as transcription factors, including B-cell lymphoma 6 protein (Bcl-6), Signal transducers and activators of transcription (STAT)1, STAT3, STAT4, B-cell activating transcription factor (Batf), interferon regulatory factor 4 (IRF4), v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (C-Maf), T-cell-specific transcription factor 1 (TCF-1) and Achaete-scute homolog 2 (Acl2), which have been shown to form a complex transcriptional network...
March 2017: Autoimmunity
https://www.readbyqxmd.com/read/28253983/micrornas-aging-cellular-senescence-and-alzheimer-s-disease
#10
P H Reddy, J Williams, F Smith, J S Bhatti, S Kumar, M Vijayan, R Kandimalla, C S Kuruva, R Wang, M Manczak, X Yin, A P Reddy
Aging is a normal process of living being. It has been reported that multiple cellular changes, including oxidative damage/mitochondrial dysfunction, telomere shortening, inflammation, may accelerate the aging process, leading to cellular senescence. These cellular changes induce age-related human diseases, including Alzheimer's, Parkinson's, multiple sclerosis, amyotrophic lateral sclerosis, cardiovascular, cancer, and skin diseases. Changes in somatic and germ-line DNA and epigenetics are reported to play large roles in accelerating the onset of human diseases...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28249802/bone-morphogenetic-proteins-in-multiple-sclerosis-role-in-neuroinflammation
#11
REVIEW
Herena Eixarch, Laura Calvo-Barreiro, Xavier Montalban, Carmen Espejo
Bone morphogenetic proteins (BMPs) are growth factors that represent the largest subgroup of signalling ligands of the transforming growth factor beta (TGF-β) superfamily. Their participation in the proliferation, survival and cell fate of several cell types and their involvement in many pathological conditions are now well known. BMP expression is altered in multiple sclerosis (MS) patients, suggesting that BMPs have a role in the pathogenesis of this disease. MS is a demyelinating and neurodegenerative autoimmune disorder of the central nervous system (CNS)...
February 27, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28203606/dna-methylation-in-oligodendroglial-cells-during-developmental-myelination-and-in-disease
#12
Sarah Moyon, Patrizia Casaccia
Oligodendrocyte progenitor cells (OPC) are the myelinating cells of the central nervous system (CNS). During development, they differentiate into mature oligodendrocytes (OL) and ensheath axons, providing trophic and functional support to the neurons. This process is regulated by the dynamic expression of specific transcription factors, which, in turn, is controlled by epigenetic marks such as DNA methylation. Here we discuss recent findings showing that DNA methylation levels are differentially regulated in the oligodendrocyte lineage during developmental myelination, affecting both genes expression and alternative splicing events...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28196884/functional-genomics-analysis-of-vitamin-d-effects-on-cd4-t-cells-in-vivo-in-experimental-autoimmune-encephalomyelitis-%C3%A2
#13
Manuel Zeitelhofer, Milena Z Adzemovic, David Gomez-Cabrero, Petra Bergman, Sonja Hochmeister, Marie N'diaye, Atul Paulson, Sabrina Ruhrmann, Malin Almgren, Jesper N Tegnér, Tomas J Ekström, André Ortlieb Guerreiro-Cacais, Maja Jagodic
Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28105729/whole-genome-grey-and-white-matter-dna-methylation-profiles-in-dorsolateral-prefrontal-cortex
#14
Jose Vicente Sanchez-Mut, Holger Heyn, Enrique Vidal, Raúl Delgado-Morales, Sebastian Moran, Sergi Sayols, Juan Sandoval, Isidre Ferrer, Manel Esteller, Johannes Gräff
The brain's neocortex is anatomically organized into grey and white matter, which are mainly composed by neuronal and glial cells, respectively. The neocortex can be further divided in different Brodmann areas according to their cytoarchitectural organization, which are associated with distinct cortical functions. There is increasing evidence that brain development and function are governed by epigenetic processes, yet their contribution to the functional organization of the neocortex remains incompletely understood...
January 20, 2017: Synapse
https://www.readbyqxmd.com/read/28093709/molecular-genetic-and-epigenetic-basis-of-multiple-sclerosis
#15
Zohreh Hojati
Multiple Sclerosis (MS) is a chronic immune-mediated disease of spinal cord and brain. The initial event in MS occurs when activated CD4(+) T cells in periphery exacerbates immune responses by stimulating immune cells such as B cells, CD8(+) cells, mast cells, granulocytes and monocytes. These proinflammatory cells pass blood brain barrier by secreting proinflammatory cytokines including TNF-α and INF-γ which activate adhesion factors. APCs (antigen-presenting cells) reactivate CD4(+) T cells after infiltrating the CNS and CD4(+) T cells produce cytokines and chemokines...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27903442/are-micrornas-true-sensors-of-ageing-and-cellular-senescence
#16
REVIEW
Justin Williams, Flint Smith, Subodh Kumar, Murali Vijayan, P Hemachandra Reddy
All living beings are programmed to death due to aging and age-related processes. Aging is a normal process of every living species. While all cells are inevitably progressing towards death, many disease processes accelerate the aging process, leading to senescence. Pathologies such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, cardiovascular disease, cancer, and skin diseases have been associated with deregulated aging. Healthy aging can delay onset of all age-related diseases...
May 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/27795849/whole-genome-dna-methylation-analysis-of-peripheral-blood-mononuclear-cells-in-multiple-sclerosis-patients-with-different-disease-courses
#17
O G Kulakova, M R Kabilov, L V Danilova, E V Popova, O A Baturina, E Y Tsareva, N M Baulina, I S Kiselev, A N Boyko, A V Favorov, O O Favorova, V V Vlassov
Multiple sclerosis (MS) is a severe neurodegenerative disease of polygenic etiology affecting the central nervous system. In addition to genetic factors, epigenetic mechanisms, primarily DNA methylation, which regulate gene expression, play an important role in MS development and progression. In this study, we have performed the first whole-genome DNA methylation profiling of peripheral blood mononuclear cells in relapsing-remitting MS (RRMS) and primary-progressive MS (PPMS) patients and compared them to those of healthy individuals in order to identify the differentially methylated CpG-sites (DMSs) associated with these common clinical disease courses...
July 2016: Acta Naturae
https://www.readbyqxmd.com/read/27709268/the-neuronal-metabolite-naa-regulates-histone-h3-methylation-in-oligodendrocytes-and-myelin-lipid-composition
#18
N K Singhal, H Huang, S Li, R Clements, J Gadd, A Daniels, E E Kooijman, P Bannerman, T Burns, F Guo, D Pleasure, E Freeman, L Shriver, J McDonough
The neuronal mitochondrial metabolite N-acetylaspartate (NAA) is decreased in the multiple sclerosis (MS) brain. NAA is synthesized in neurons by the enzyme N-acetyltransferase-8-like (NAT8L) and broken down in oligodendrocytes by aspartoacylase (ASPA) into acetate and aspartate. We have hypothesized that NAA links the metabolism of axons with oligodendrocytes to support myelination. To test this hypothesis, we performed lipidomic analyses using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high-performance thin-layer chromatography (HPTLC) to identify changes in myelin lipid composition in postmortem MS brains and in NAT8L knockout (NAT8L(-/-)) mice which do not synthesize NAA...
January 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/27698367/mir-125a-3p-timely-inhibits-oligodendroglial-maturation-and-is-pathologically-up-regulated-in-human-multiple-sclerosis
#19
Davide Lecca, Davide Marangon, Giusy T Coppolino, Aida Menéndez Méndez, Annamaria Finardi, Gloria Dalla Costa, Vittorio Martinelli, Roberto Furlan, Maria P Abbracchio
In the mature central nervous system (CNS), oligodendrocytes provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, oligodendroglial precursors (OPCs) follow a very precise differentiation program, which is finely orchestrated by transcription factors, epigenetic factors and microRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional regulation. Any alterations in this program can potentially contribute to dysregulated myelination, impaired remyelination and neurodegenerative conditions, as it happens in multiple sclerosis (MS)...
October 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27651245/epigenetic-modifications-in-neurological-diseases-natural-products-as-epigenetic-modulators-a-treatment-strategy
#20
Omkaram Gangisetty, Sengottuvelan Murugan
Epigenetic modifications, including DNA methylation, covalent histone modifications, and small noncoding RNAs, play a key role in regulating the gene expression. This regulatory mechanism is important in cellular differentiation and development. Recent advances in the field of epigenetics extended the role of epigenetic mechanisms in controlling key biological processes such as genome imprinting and X-chromosome inactivation. Aberrant epigenetic modifications are associated with the development of many diseases...
2016: Advances in Neurobiology
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