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Myelin regulatory factor

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https://www.readbyqxmd.com/read/28631093/myelin-regulatory-factor-drives-remyelination-in-multiple-sclerosis
#1
Greg J Duncan, Jason R Plemel, Peggy Assinck, Sohrab B Manesh, Fraser G W Muir, Ryan Hirata, Matan Berson, Jie Liu, Michael Wegner, Ben Emery, G R Wayne Moore, Wolfram Tetzlaff
Remyelination is limited in the majority of multiple sclerosis (MS) lesions despite the presence of oligodendrocyte precursor cells (OPCs) in most lesions. This observation has led to the view that a failure of OPCs to fully differentiate underlies remyelination failure. OPC differentiation requires intricate transcriptional regulation, which may be disrupted in chronic MS lesions. The expression of few transcription factors has been differentially compared between remyelinating lesions and lesions refractory to remyelination...
June 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28623291/crystal-structure-of-the-dna-binding-domain-of-myelin-gene-regulatory-factor
#2
Xiangkai Zhen, Bowen Li, Fen Hu, Shufeng Yan, Gabriele Meloni, Huiliang Li, Ning Shi
Myelin-gene Regulatory Factor (MyRF) is one of the master transcription factors controlling myelin formation and development in oligodendrocytes which is crucial for the powerful brain functions. The N-terminal of MyRF, which contains a proline-rich region and a DNA binding domain (DBD), is auto-cleaved from the ER membrane, and then enters the nucleus to participate in transcription regulation of the myelin genes. Here we report the crystal structure of MyRF DBD. It shows an Ig-fold like architecture which consists of two antiparallel β-sheets with 7 main strands, packing against each other, forming a β-sandwich...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28594147/casein-kinase-1-epsilon-deletion-increases-mu-opioid-receptor-dependent-behaviors-and-binge-eating
#3
Lisa R Goldberg, Stacey L Kirkpatrick, Neema Yazdani, Kimberly P Luttik, Olga A Lacki, R Keith Babbs, David F Jenkins, W Evan Johnson, Camron D Bryant
Genetic and pharmacological studies indicate that casein kinase-1 epsilon (Csnk1e) contributes to psychostimulant, opioid, and ethanol motivated behaviors. We previously used pharmacological inhibition to demonstrate that Csnk1e negatively regulates the locomotor stimulant properties of opioids and psychostimulants. Here, we tested the hypothesis that Csnk1e negatively regulates opioid and psychostimulant reward using genetic inhibition and the conditioned place preference assay in Csnk1e knockout mice. Similar to pharmacological inhibition, Csnk1e knockout mice showed enhanced opioid-induced locomotor activity with the mu opioid receptor agonist fentanyl (0...
June 8, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28549068/oligodendroglial-myelination-requires-astrocyte-derived-lipids
#4
Nutabi Camargo, Andrea Goudriaan, Anne-Lieke F van Deijk, Willem M Otte, Jos F Brouwers, Hans Lodder, David H Gutmann, Klaus-Armin Nave, Rick M Dijkhuizen, Huibert D Mansvelder, Roman Chrast, August B Smit, Mark H G Verheijen
In the vertebrate nervous system, myelination of axons for rapid impulse propagation requires the synthesis of large amounts of lipids and proteins by oligodendrocytes and Schwann cells. Myelin membranes are thought to be cell-autonomously assembled by these axon-associated glial cells. Here, we report the surprising finding that in normal brain development, a substantial fraction of the lipids incorporated into central nervous system (CNS) myelin are contributed by astrocytes. The oligodendrocyte-specific inactivation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), an essential coactivator of the transcription factor SREBP and thus of lipid biosynthesis, resulted in significantly retarded CNS myelination; however, myelin appeared normal at 3 months of age...
May 2017: PLoS Biology
https://www.readbyqxmd.com/read/28452087/cytotoxic-cd8-t-cells-ablation-enhances-the-capacity-of-regulatory-t-cells-to-delay-viral-elimination-in-theiler-s-murine-encephalomyelitis
#5
Malgorzata Ciurkiewicz, Vanessa Herder, Muhammad Akram Khan, Ann-Kathrin Uhde, René Teich, Stephan Floess, Wolfgang Baumgärtner, Jochen Huehn, Andreas Beineke
Theiler's murine encephalomyelitis (TME) of susceptible mouse strains is a commonly used infectious animal model for multiple sclerosis. The study aim was to test the hypothesis whether cytotoxic T cell responses account for the limited impact of regulatory T cells on antiviral immunity in TME virus-induced demyelinating disease (TMEV-IDD) resistant C57BL/6 mice. TME virus-infected C57BL/6 mice were treated with (i) interleukin-2/-anti-interleukin-2-antibody-complexes to expand regulatory T cells ('Treg-expansion'), (ii) anti-CD8-antibodies to deplete cytotoxic T cells ('CD8-depletion') or (iii) with a combination of Treg-expansion and CD8-depletion ('combined treatment') prior to infection...
April 27, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28423529/pif-promotes-brain-re-myelination-locally-while-regulating-systemic-inflammation-clinically-relevant-multiple-sclerosis-m-smegmatis-model
#6
Giuseppe Migliara, Martin Mueller, Alessia Piermattei, Chaya Brodie, Michael J Paidas, Eytan R Barnea, Francesco Ria
Neurologic disease diagnosis and treatment is challenging. Multiple Sclerosis (MS) is a demyelinating autoimmune disease with few clinical forms and uncertain etiology. Current studies suggest that it is likely caused by infection(s) triggering a systemic immune response resulting in antigen/non-antigen-related autoimmune response in central nervous system (CNS). New therapeutic approaches are needed. Secreted by viable embryos, PreImplantation Factor (PIF) possesses a local and systemic immunity regulatory role...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28370559/transcription-factor-sox10-regulates-oligodendroglial-sox9-levels-via-micrornas
#7
Simone Reiprich, Martina Cantone, Matthias Weider, Tina Baroti, Jan Wittstatt, Christian Schmitt, Melanie Küspert, Julio Vera, Michael Wegner
During development of myelin-forming oligodendrocytes in the central nervous system the two closely related transcription factors Sox9 and Sox10 play essential roles that are partly shared and partly unique. Whereas Sox9 primarily functions during oligodendroglial specification, Sox10 is uniquely required to induce terminal differentiation and myelination. During this process, Sox10 protein levels rise substantially. As this coincides with a reciprocal decrease in Sox9, we postulated that Sox10 influences Sox9 amounts in differentiating oligodendrocytes...
April 3, 2017: Glia
https://www.readbyqxmd.com/read/28214347/involvement-of-the-guanine-nucleotide-exchange-factor-vav3-in-central-nervous-system-development-and-plasticity
#8
REVIEW
Annika Ulc, Christine Gottschling, Ina Schäfer, David Wegrzyn, Simon van Leeuwen, Veronika Luft, Jacqueline Reinhard, Andreas Faissner
Small GTP-hydrolyzing enzymes (GTPases) of the RhoA family play manifold roles in cell biology and are regulated by upstream guanine nucleotide exchange factors (GEFs). Herein, we focus on the GEFs of the Vav subfamily. Vav1 was originally described as a proto-oncogene of the hematopoietic lineage. The GEFs Vav2 and Vav3 are more broadly expressed in various tissues. In particular, the GEF Vav3 may play important roles in the developing nervous system during the differentiation of neural stem cells into the major lineages, namely neurons, oligodendrocytes and astrocytes...
May 1, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28203609/zeb2-inhibiting-the-inhibitors-in-schwann-cells
#9
Bastian G Brinkmann, Susanne Quintes
Development of Schwann cells is tightly regulated by concerted action of activating and inhibiting factors. Most of the regulatory feedback loops identified to date are transcriptional activators promoting induction of genes coding for integral myelin proteins and lipids. The mechanisms by which inhibitory factors are silenced during Schwann cell maturation are less well understood. We could recently show a pivotal function for the transcription factor zinc finger E-box binding homeobox 2 (Zeb2) during Schwann cell development and myelination as a transcriptional repressor of maturation inhibitors...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28193689/signaling-by-fgf-receptor-2-not-fgf-receptor-1-regulates-myelin-thickness-through-activation-of-erk1-2-mapk-which-promotes-mtorc1-activity-in-an-akt-independent-manner
#10
Miki Furusho, Akihiro Ishii, Rashmi Bansal
FGF signaling has emerged as a significant "late-stage" regulator of myelin thickness in the CNS, independent of oligodendrocyte differentiation. Therefore, it is critically important to identify the specific FGF receptor type and its downstream signaling molecules in oligodendrocytes to obtain better insights into the regulatory mechanisms of myelin growth. Here, we show that FGF receptor type 2 (FGFR2) is highly enriched at the paranodal loops of myelin. Conditional ablation of this receptor-type, but not FGF receptor type 1 (FGFR1), resulted in attenuation of myelin growth, expression of major myelin genes, key transcription factor Myrf and extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) activity...
March 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28130959/evidence-of-altered-brain-regulatory-gene-expression-in-tobacco-exposed-fetuses
#11
Hamisu M Salihu, Arnut Paothong, Rachita Das, Lindsey M King, Anupam Pradhan, Bridget Riggs, Eknath Naik, Erin M Siegel, Valerie E Whiteman
AIM: We sought to determine the association between prenatal smoking status and expression of fetal brain regulatory genes. METHODS: At delivery, we collected information from parturient women on prenatal smoking habits and analyzed salivary cotinine levels. We obtained neonatal umbilical cord blood and extracted total RNA. We then employed the quantitative polymerase chain reaction (QPCR) analyses and the comparative CT method to calculate the relative gene expression of selected fetal brain regulatory genes responsible for (1) brain growth (brain-derived neutrotrophic factor, BDNF), (2) myelination (proteolipidic protein 1, PLP1 and myelin basic protein, MBP), and (3) neuronal migration and cell-cell interactions during fetal brain development or RLN...
January 28, 2017: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/28077718/integrin-linked-kinase-ilk-deletion-disrupts-oligodendrocyte-development-by-altering-cell-cycle
#12
Rashad Hussain, Wendy B Macklin
During development, oligodendrocytes are initially specified, after which oligodendrocyte precursor cells (OPCs) migrate and proliferate before differentiating into myelinating cells. Lineage-specific programming of oligodendrocytes results from sensing environmental cues through membrane-bound receptors and related intracellular signaling molecules. Integrin-linked kinase (ILK) is an important protein that is expressed at the inner margins of the plasma membrane and can mediate some of these signals. The current studies demonstrate that ILK deletion reduces the proliferation and differentiation of OPCs in the developing CNS...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28065579/roles-of-regulatory-t-cells-and-il-10-in-virus-induced-demyelination
#13
REVIEW
Stanley Perlman, Jingxian Zhao
Neurotropic viruses are important causes of morbidity and mortality in human populations. Some of these viruses preferentially infect oligodendrocytes in the white matter, causing either direct lysis of infected cells, or more commonly myelin damage as a consequence of the host immune response to the virus. Virus-induced demyelination has similarities to the human disease multiple sclerosis. To study this disease process in experimental animals, mice are infected, most commonly, with neurotropic strains of mouse hepatitis virus, a coronavirus or Theiler's murine encephalomyelitis, a picornavirus...
July 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28051239/ex-vivo-expansion-of-antigen-specific-cd4-cd25-regulatory-t-cells-from-autologous-na%C3%A3-ve-cd4-t-cells-of-multiple-sclerosis-patients-as-a-potential-therapeutic-approach
#14
Y-J Xiang, M Ren, H Jiang, T-T Yang, Y He, D-H Ao, Y-Y Wang, Q Zhang, X-J He, X-G Gao, G-Z Liu
OBJECTIVE: CD4+CD25+ regulatory T cells (Tregs) have been found to have a decreased effector function in patients with multiple sclerosis (MS). In this study, we co-cultured naïve CD4+ T cells of MS patients with myelin basic protein (MBP)85-99 peptide as specific antigen and allogenic B cells as antigen-presenting cells, in an attempt to generate adequate antigen-specific CD4+CD25+ Tregs with normal or improved immune function. PATIENTS AND METHODS: Naïve CD4+ T cells were isolated from peripheral blood mononuclear cells (PBMCs) from patients with MS (n=5) and healthy controls (HC, n=5)...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27973735/the-role-of-p38alpha-in-schwann-cells-in-regulating-peripheral-nerve-myelination-and-repair
#15
Sheridan L Roberts, Xin-Peng Dun, Gemma Dee, Bethany Gray, Thomas Mindos, David B Parkinson
Myelination in the peripheral nervous system (PNS) is controlled by both positive and negative regulators within Schwann cells to ensure timely onset and correct myelin thickness for saltatory conduction by neurons. Transcription factors such as Sox10, octamer-binding transcription factor 6 (Oct6) and Krox20 form a positive regulatory network, whereas negative regulators such as cJun and Sox2 oppose myelination in Schwann cells. The role of the p38 MAPK pathway has been studied in PNS myelination, but its precise function remains unclear, with both positive and negative effects of p38 activity reported upon both myelination and processes of nerve repair...
April 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27913589/integrin-linked-kinase-ilk-deletion-disrupts-oligodendrocyte-development-by-altering-cell-cycle
#16
Rashad Hussain, Wendy B Macklin
During development, oligodendrocytes are initially specified, after which oligodendrocyte precursor cells (OPCs) migrate and proliferate before differentiating into myelinating cells. Lineage specific programming of oligodendrocytes results from sensing environmental cues through membrane-bound receptors and related intracellular signaling molecules. Integrin linked kinase (ILK) is an important protein expressed at the inner margins of the plasma membrane, which can mediate some of these signals. The current studies demonstrate that ILK deletion reduces the proliferation and differentiation of OPCs in the developing CNS...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27889898/the-transcription-factors-ebf1-and-ebf2-are-positive-regulators-of-myelination-in-schwann-cells
#17
Diego Moruzzo, Lucilla Nobbio, Bruno Sterlini, G Giacomo Consalez, Fabio Benfenati, Angelo Schenone, Anna Corradi
Myelin formation by Schwann cells is tightly controlled by multiple pathways and regulatory molecules. The Ebf2 gene, belonging to the Ebf family of transcription factors regulating cell development and differentiation, is expressed in Schwann cells, and Ebf2 knockout mice show peripheral nerve defects. We also found that Ebf1 is expressed in Schwann cells. To investigate Ebf function in myelination, we silenced Ebf genes in myelinating dorsal root ganglia cultures. Combined downregulation of Ebf genes leads to a severe impairment of myelin formation that is completely rescued by their specific overexpression, suggesting that the expression level of Ebf genes strongly influences axon myelination...
November 26, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27829268/altered-translational-control-of-fragile-x-mental-retardation-protein-on-myelin-proteins-in-neuropsychiatric-disorders
#18
REVIEW
Se Jin Jeon, Jong Hoon Ryu, Geon Ho Bahn
Myelin is a specialized structure of the nervous system that both enhances electrical conductance and insulates neurons from external risk factors. In the central nervous system, polarized oligodendrocytes form myelin by wrapping processes in a spiral pattern around neuronal axons through myelin-related gene regulation. Since these events occur at a distance from the cell body, post-transcriptional control of gene expression has strategic advantage to fine-tune the overall regulation of protein contents in situ...
May 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27771555/srebf-2-polymorphism-influences-white-matter-microstructure-in-bipolar-disorder
#19
Sara Poletti, Veronica Aggio, Irene Bollettini, Andrea Falini, Cristina Colombo, Francesco Benedetti
The aim of the study is to investigate if gene polymorphisms in sterol regulatory element binding protein transcriptional factors SREBF-1 and SREBF-2, which regulate lipid and cholesterol metabolism, could affect white matter (WM) microstructure, the most recognized structural biomarker of bipolar disorder (BD). In a sample of 93 patients affected by BD, we investigated the effect of SREBF-1 rs11868035, and SREBF-2 rs1052717, on WM microstructure, using diffusion tensor imaging and tract-based spatial statistics...
October 15, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27733608/olig2-targeted-g-protein-coupled-receptor-gpr17-regulates-oligodendrocyte-survival-in-response-to-lysolecithin-induced-demyelination
#20
Zhimin Ou, Yuxia Sun, Li Lin, Nachun You, Xue Liu, Hongchao Li, Yanchen Ma, Lei Cao, Ying Han, Min Liu, Yaqi Deng, Luming Yao, Q Richard Lu, Ying Chen
Demyelinating diseases, such as multiple sclerosis, are known to result from acute or chronic injury to the myelin sheath and inadequate remyelination; however, the underlying molecular mechanisms remain unclear. Here, we performed genome occupancy analysis by chromatin immunoprecipitation sequencing in oligodendrocytes in response to lysolecithin-induced injury and found that Olig2 and its downstream target Gpr17 are critical factors in regulating oligodendrocyte survival. After injury to oligodendrocytes, Olig2 was significantly upregulated and transcriptionally targeted the Gpr17 locus...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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