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Myelin regulatory factor

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https://www.readbyqxmd.com/read/27913589/integrin-linked-kinase-ilk-deletion-disrupts-oligodendrocyte-development-by-altering-cell-cycle
#1
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...
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
#2
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-fmrp-on-myelin-proteins-in-neuropsychiatric-disorders
#3
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...
November 8, 2016: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27771555/srebf-2-polymorphism-influences-white-matter-microstructure-in-bipolar-disorder
#4
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
#5
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
https://www.readbyqxmd.com/read/27708418/b-cell-derived-transforming-growth-factor-%C3%AE-1-expression-limits-the-induction-phase-of-autoimmune-neuroinflammation
#6
Kristbjörg Bjarnadóttir, Mahdia Benkhoucha, Doron Merkler, Martin S Weber, Natalie L Payne, Claude C A Bernard, Nicolas Molnarfi, Patrice H Lalive
Studies in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), have shown that regulatory B cells modulate the course of the disease via the production of suppressive cytokines. While data indicate a role for transforming growth factor (TGF)-β1 expression in regulatory B cell functions, this mechanism has not yet been tested in autoimmune neuroinflammation. Transgenic mice deficient for TGF-β1 expression in B cells (B-TGF-β1(-/-)) were tested in EAE induced by recombinant mouse myelin oligodendrocyte glycoprotein (rmMOG)...
October 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27597394/progesterone-treatment-modulates-mrna-of-neurosteroidogenic-enzymes-in-a-murine-model-of-multiple-sclerosis
#7
Laura Garay, Paula Gonzalez Giqueaux, Rachida Guennoun, Michael Schumacher, Maria Claudia Gonzalez Deniselle, Alejandro F De Nicola
Previous studies of experimental autoimmune encephalomyelitis (EAE) have shown that progesterone decreases inflammatory cell infiltration and proinflammatory factors, increases myelination and attenuates clinical grade of EAE mice. To elucidate potential mediators of these effects, we analyzed the mRNA expression of neurosteroidogenic enzymes in the spinal cord, in view of the protective role of steroids in EAE. We also analyzed mitochondrial morphology and dynamics (fusion and fission proteins), considering the role of mitochondria in neurosteroidogenesis...
January 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27572856/immunopathophysiology-of-pediatric-cns-inflammatory-demyelinating-diseases
#8
Amit Bar-Or, Rogier Q Hintzen, Russell C Dale, Kevin Rostasy, Wolfgang Brück, Tanuja Chitnis
Elucidating pathophysiologic mechanisms underlying the spectrum of pediatric-onset CNS demyelinating diseases, particularly those that may distinguish multiple sclerosis (MS) from other entities, promises to both improve diagnostics and guide more-informed therapeutic decisions. Observations that pediatric- and adult-onset MS share the same genetic and environmental risk factors support the view that these conditions represent essentially the same illness manifesting at different ages. Nonetheless, special consideration must be given when CNS inflammation manifests in early life, at a time when multiple organs (including immune and nervous systems) are actively maturing...
August 30, 2016: Neurology
https://www.readbyqxmd.com/read/27492885/genetic-evidence-for-a-role-of-the-srebp-transcription-system-and-lipid-biosynthesis-in-schizophrenia-and-antipsychotic-treatment
#9
Vidar M Steen, Silje Skrede, Tatiana Polushina, Miguel López, Ole A Andreassen, Johan Fernø, Stephanie Le Hellard
Schizophrenia is a serious psychotic disorder, with disabling symptoms and markedly reduced life expectancy. The onset is usually in late adolescence or early adulthood, which in time overlaps with the maturation of the brain including the myelination process. Interestingly, there seems to be a link between myelin abnormalities and schizophrenia. The oligodendrocyte-derived myelin membranes in the CNS are highly enriched for lipids (cholesterol, phospholipids and glycosphingolipids), thereby pointing at lipid homeostasis as a relevant target for studying the genetics and pathophysiology of schizophrenia...
August 1, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27466180/sox10-regulates-an-alternative-promoter-at-the-charcot-marie-tooth-disease-locus-mtmr2
#10
Elizabeth A Fogarty, Megan H Brewer, Jose F Rodriguez-Molina, William D Law, Ki H Ma, Noah M Steinberg, John Svaren, Anthony Antonellis
Schwann cells are the myelinating glia of the peripheral nervous system and dysfunction of these cells causes motor and sensory peripheral neuropathy. The transcription factor SOX10 is critical for Schwann cell development and maintenance, and many SOX10 target genes encode proteins required for Schwann cell function. Loss-of-function mutations in the gene encoding myotubularin related protein 2 (MTMR2) cause Charcot-Marie-Tooth disease type 4B1 (CMT4B1), a severe demyelinating peripheral neuropathy characterized by myelin outfoldings along peripheral nerves...
July 27, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27462272/activation-of-sterol-regulatory-element-binding-factors-by-fenofibrate-and-gemfibrozil-stimulates-myelination-in-zebrafish
#11
Yoshifumi Ashikawa, Yuhei Nishimura, Shiko Okabe, Shota Sasagawa, Soichiro Murakami, Mizuki Yuge, Koki Kawaguchi, Reiko Kawase, Toshio Tanaka
Oligodendrocytes are major myelin-producing cells and play essential roles in the function of a healthy nervous system. However, they are also one of the most vulnerable neural cell types in the central nervous system (CNS), and myelin abnormalities in the CNS are found in a wide variety of neurological disorders, including multiple sclerosis, adrenoleukodystrophy, and schizophrenia. There is an urgent need to identify small molecular weight compounds that can stimulate myelination. In this study, we performed comparative transcriptome analysis to identify pharmacodynamic effects common to miconazole and clobetasol, which have been shown to stimulate myelination by mouse oligodendrocyte progenitor cells (OPCs)...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27455109/rapid-production-of-new-oligodendrocytes-is-required-in-the-earliest-stages-of-motor-skill-learning
#12
Lin Xiao, David Ohayon, Ian A McKenzie, Alexander Sinclair-Wilson, Jordan L Wright, Alexander D Fudge, Ben Emery, Huiliang Li, William D Richardson
We identified mRNA encoding the ecto-enzyme Enpp6 as a marker of newly forming oligodendrocytes, and used Enpp6 in situ hybridization to track oligodendrocyte differentiation in adult mice as they learned a motor skill (running on a wheel with unevenly spaced rungs). Within just 2.5 h of exposure to the complex wheel, production of Enpp6-expressing immature oligodendrocytes was accelerated in subcortical white matter; within 4 h, it was accelerated in motor cortex. Conditional deletion of myelin regulatory factor (Myrf) in oligodendrocyte precursors blocked formation of new Enpp6(+) oligodendrocytes and impaired learning within the same ∼2-3 h time frame...
September 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27435985/nanoparticle-delivered-irf5-sirna-facilitates-m1-to-m2-transition-reduces-demyelination-and-neurofilament-loss-and-promotes-functional-recovery-after-spinal-cord-injury-in-mice
#13
Jun Li, Yanbin Liu, Haidong Xu, Qiang Fu
Macrophage activation and persistent inflammation contribute to the pathogenesis of spinal cord injury (SCI), and different phenotypes of macrophages play diverse roles in the pathological process of SCI. After SCI, there is an acute phase of alternatively activated (M2) macrophage infiltration, followed by a long-lasting phase of classically activated (M1) macrophage accumulation in the wound. The long-lasting predominance of M1 macrophages may derail healing and compromise organ functions. Based on the previous findings that the transcription factor interferon regulatory factor 5 (IRF5) up-regulates genes associated with M1 macrophages, we attempted to examine the effect of silencing IRF5 on SCI progression...
October 2016: Inflammation
https://www.readbyqxmd.com/read/27385127/reduced-sterol-regulatory-element-binding-protein-srebp-processing-through-site-1-protease-s1p-inhibition-alters-oligodendrocyte-differentiation-in-vitro
#14
Hubert Monnerie, Micah Romer, Brigid K Jensen, John S Millar, Kelly L Jordan-Sciutto, Sangwon F Kim, Judith B Grinspan
The formation of the myelin membrane of the oligodendrocyte in the CNS is a fundamental process requiring the coordinated synthesis of many different components. The myelin membrane is particularly rich in lipids, however, the regulation of these synthesis of these is not understood. In other cell types, including Schwann cells, the myelin-forming cells of the PNS, lipid synthesis is tightly regulated by the sterol regulatory element-binding protein (SREBP) family of transcription factors, but this has not been previously shown in oligodendrocytes...
July 6, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27370227/co-transplantation-of-mrf-overexpressing-oligodendrocyte-precursor-cells-and-schwann-cells-promotes-recovery-in-rat-after-spinal-cord-injury
#15
Xiu-Mei Xie, Ling-Ling Shi, Lin Shen, Rui Wang, Qi Qi, Qi-Yi Wang, Lun-Jun Zhang, He-Zuo Lü, Jian-Guo Hu
Oligodendrocyte (OL) replacement is a promising treatment strategy for spinal cord injury (SCI). However, the poor survival of transplanted OLs or their precursors and inhibition of axonal regeneration are two major challenges with this approach. Our previous study showed that Schwann cells (SCs) promoted survival, proliferation, and migration of transplanted OL progenitor cells (OPCs) and neurological recovery. Remyelination is an important basis for functional recovery following spinal cord injury. It has been reported that myelin gene regulatory factor (MRF), a transcriptional regulator which specifically is expressed in postmitotic OLs within the CNS, is essential for OL maturation and CNS myelination...
October 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27342760/regulation-of-oligodendrocyte-differentiation-insights-and-approaches-for-the-management-of-neurodegenerative-disease
#16
REVIEW
Abdullah Mohammad Tauheed, Joseph Olusegun Ayo, Mohammed Umaru Kawu
The development and maturation of oligodendrocyte require complex mechanisms that interact at different levels to regulate neuronal activities. This review examines specific functions and critical roles of oligodendrocyte, regulatory factors involved in its differentiation, including the involvement of glutamate and reactive oxygen species (ROS). Olig2, Id4, Wnt/β-catenin and histone deacetylase (HDAC) appear to play crucial roles in spatio-temporal regulation of the differentiation of oligodendrocytes. Furthermore, HDAC appears to be the rate-limiting factor that may be manipulated to promote myelination as it simultaneously allays contact inhibition of Id4 in the intrinsic pathway and Wnt/β-catenin in the extrinsic pathway...
September 2016: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/27256343/pathways-and-gene-networks-mediating-the-regulatory-effects-of-cannabidiol-a-nonpsychoactive-cannabinoid-in-autoimmune-t-cells
#17
Ewa Kozela, Ana Juknat, Fuying Gao, Nathali Kaushansky, Giovanni Coppola, Zvi Vogel
BACKGROUND: Our previous studies showed that the non-psychoactive cannabinoid, cannabidiol (CBD), ameliorates the clinical symptoms in mouse myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis model of multiple sclerosis (MS) as well as decreases the memory MOG35-55-specific T cell (TMOG) proliferation and cytokine secretion including IL-17, a key autoimmune factor. The mechanisms of these activities are currently poorly understood. METHODS: Herein, using microarray-based gene expression profiling, we describe gene networks and intracellular pathways involved in CBD-induced suppression of these activated memory TMOG cells...
2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27243011/regenerative-capacity-of-macrophages-for-remyelination
#18
REVIEW
Khalil S Rawji, Manoj K Mishra, V Wee Yong
White matter injury, consisting of loss of axons, myelin, and oligodendrocytes, is common in many neurological disorders and is believed to underlie several motor and sensory deficits. Remyelination is the process in which the insulative myelin sheath is restored to axons, thereby facilitating recovery from functional loss. Remyelination proceeds with oligodendrocyte precursor cells (OPCs) that differentiate into oligodendrocytes to synthesize the new myelin sheath after demyelination. This process is influenced by several factors, including trophic factors, inhibitory molecules in the lesion microenvironment, age of the subject, as well as the inflammatory response...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/26956729/epstein-barr-virus-and-mycobacterium-avium-subsp-paratuberculosis-peptides-are-recognized-in-sera-and-cerebrospinal-fluid-of-ms-patients
#19
Giuseppe Mameli, Eleonora Cocco, Jessica Frau, Maria Giovanna Marrosu, Leonardo Antonio Sechi
Mycobacterium avium subsp. paratuberculosis (MAP) and Epstein-Barr virus (EBV) epitopes elicit a consistent humoral response in serum of multiple sclerosis patients, but the cross reactivity against the homologous myelin basic protein (MBP) and human interferon regulatory factor 5 (IRF5) has not been searched within the Cerebral Spinal Fluid (CSF). We evaluated in sera and CSF of patients with MS and with other neurological diseases (OND) the humoral response against EBV/MAP peptides and the IRF5/MBP. Our data showed that EBV and MAP peptides are able to induce a specific humoral immune response in MS patients compared to OND controls both in serum and in CSF...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26953870/immunologic-effects-of-metformin-and-pioglitazone-treatment-on-metabolic-syndrome-and-multiple-sclerosis
#20
Laura Negrotto, Mauricio F Farez, Jorge Correale
IMPORTANCE: Metabolic syndrome (MetS) is thought to influence several autoimmune diseases, including multiple sclerosis (MS). Anti-inflammatory effects of treatments used for MetS, such as metformin hydrochloride and pioglitazone hydrochloride, have been demonstrated, although clinical evidence supporting use of these treatments in MS is lacking. OBJECTIVES: To determine whether metformin and/or pioglitazone are associated with a reduction in disease activity as measured by brain magnetic resonance imaging in patients with MS and MetS and to evaluate the potential mechanisms underlying this anti-inflammatory effect...
May 1, 2016: JAMA Neurology
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