DOCSLIB.ORG

Myelin Fat Facts: an Overview of Lipids and Fatty Acid Metabolism

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Myelin Fat Facts: an Overview of Lipids and Fatty Acid Metabolism cells Review Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism Yannick Poitelon , Ashley M. Kopec and Sophie Belin * Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY 12208, USA; [email protected] (Y.P.); [email protected] (A.M.K.) * Correspondence: [email protected] Received: 5 March 2020; Accepted: 25 March 2020; Published: 27 March 2020 Abstract: Myelin is critical for the proper function of the nervous system and one of the most complex cell–cell interactions of the body. Myelination allows for the rapid conduction of action potentials along axonal fibers and provides physical and trophic support to neurons. Myelin contains a high content of lipids, and the formation of the myelin sheath requires high levels of fatty acid and lipid synthesis, together with uptake of extracellular fatty acids. Recent studies have further advanced our understanding of the metabolism and functions of myelin fatty acids and lipids. In this review, we present an overview of the basic biology of myelin lipids and recent insights on the regulation of fatty acid metabolism and functions in myelinating cells. In addition, this review may serve to provide a foundation for future research characterizing the role of fatty acids and lipids in myelin biology and metabolic disorders affecting the central and peripheral nervous system. Keywords: Schwann cell; oligodendrocyte; myelin; lipid; fatty acid 1. Introduction Myelin is a specialized multilamellar membrane consisting of 40 or more tightly wrapped lipid bilayers [1]. The deposition of compact myelin in a spiraling pattern around an axon generates two morphological features that can be observed by electron microscopy, (1) the major dense line (MDL), which is the tight apposition of the cytoplasmic leaflets, and (2) the intraperiod line (IPL), which is the apposition of the extracellular leaflets (Figure1). Myelin is made by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). CNS and PNS myelin differ in several important ways. One oligodendrocyte forms myelin sheath segments for several neurons, whereas a single Schwann cell myelinates one segment for a single neuron. During the development of the vertebrate nervous system, myelination starts around birth first in the PNS, then the spinal cord and finally in the brain. Although most myelination will be completed in the PNS shortly after birth (within two years after birth in humans; within four weeks after birth in rodents), myelination in the CNS is an ongoing process that continues throughout adulthood. During active CNS myelination in rodents, the myelin sheath expands at a rate 5 103 – 5 104 µm2/cell/day (15 × × to 150 times faster than a normal cell body membrane extension). In addition, one oligodendrocyte or one Schwann cell supports a surface area of myelin up to 2 mm2 or 20 mm2 respectively, which can represent 2000 times the cell surface area of an epithelial cell [2,3]. Although the turnover of myelin lipids in humans is uncharacterized, studies in mice showed that lipids within the myelin sheath are continuously remodeled, and lipid turnover rates are differently regulated through life [4]. Thus, biosynthesis, storage, and cellular trafficking of myelin lipids are essential to the assembly and maintenance of myelin in the nervous system through life span. Recent reviews have provided updates on the genes, proteins, and molecular signals controlling myelination both in the PNS and CNS [5–7]. Herein, we focus on the most recent developments regarding myelin lipids and fatty acids. Cells 2020, 9, 812; doi:10.3390/cells9040812 www.mdpi.com/journal/cells Cells 2020, 9, x FOR PEER REVIEW 2 of 17 Cells 2020updates, 9, 812 on the genes, proteins, and molecular signals controlling myelination both in the PNS and 2 of 17 CNS [5–7]. Herein, we focus on the most recent developments regarding myelin lipids and fatty acids. Figure 1.FigureThe 1. structure The structure of peripheral of peripheral nervous nervous systemsystem myelin myelin sheath. sheath. Schematic Schematic representation representation of a (i) of a (i) myelinated axon, (ii) myelin sheath, (iii) bilayer membrane, and (iv) major lipids classes. Myelin is myelinated axon, (ii) myelin sheath, (iii) bilayer membrane, and (iv) major lipids classes. Myelin is formed by apposition of the external surfaces and internal surfaces of the myelin bilayer that formedconstitute by apposition the intraperiodic of the external line (IPL) surfaces and the and major internal dense line surfaces (MDL), of respectively the myelin (ii, bilayer iii). The thatmyelin constitute the intraperiodicbilayer has linean asymmetric (IPL) and thelipid major composition dense line(iii, (MDL),iv). Myelin respectively protein are ( iialso, iii ).asymmetrically The myelin bilayer has an asymmetricdistributed with lipid for example composition PLP and ( iiiP0, iniv the). IP MyelinL and MBP protein and PMP2 are also at the asymmetrically MDL (iii). Cholesterol distributed with for(Chl.), example Galactosylceramide PLP and P0 in(Galc, the cyan), IPL andPlasmalogen MBP and (PE, PMP2 yellow), at Phosphatidylcholine the MDL (iii). Cholesterol (PC, dark (Chl.), Galactosylceramideblue), Sphingomyelin (Galc, (SM, cyan), light Plasmalogenblue) and other (PE,phospholipids yellow), (PL, Phosphatidylcholine red). P0, PMP2 proteins (PC, and dark the blue), enrichment of sphingomyelin in the myelin are specific to PNS myelin. Sphingomyelin (SM, light blue) and other phospholipids (PL, red). P0, PMP2 proteins and the enrichment2. Myelin of Lipids sphingomyelin—Role of Lipids in the in myelin Myelin are specific to PNS myelin. 2. Myelin Lipids—RoleThe myelin sheath of is Lipids characterized in Myelin by a high proportion of lipids (70%–85%) and consequently a low proportion of proteins (15%–30%). In contrast, most biological membranes have approximatively Theequivalent myelin ratio sheath of proteins is characterized to lipids (50% by lipid a high/50%proportion protein) [8]. T ofhe lipidshigh lipid/protein (70%–85%) ratio and in consequentlymyelin a low proportioncontributes ofto proteinsthe close (15%–30%).packing and tight In contrast, organization most of biological the myelin membranes sheath through have non approximatively-covalent equivalentinteractions ratio of between proteins lipids to and lipids myelin (50% proteins lipid/ [9]50%. In protein)addition, the [8]. enrichment The high in lipid specific/protein classes ratioof lipids in myelin contributesis also to required the close for the packing long-term and maintenance tight organization of myelin [10] of. The the three myelin major sheathclasses of through membrane non-covalent lipids are cholesterol, phospholipids (e.g., plasmalogen, lecithin, sphingomyelin) and glycolipids (e.g., interactions between lipids and myelin proteins [9]. In addition, the enrichment in specific classes of galactosylceramide). The lipid composition of myelin sheath is distinctive, made of high amounts of lipids ischolesterol also required and forenriched the long-term in glycolipid, maintenance in a ratio ofof myelin 40%:40%:20% [10]. The(cholesterol, three major phospholipid classes of, and membrane lipids areglycolipid, cholesterol, respectively) phospholipids compared to (e.g., most plasmalogen, biological membranes lecithin, (25%:65%:10% sphingomyelin)) [11]. and glycolipids (e.g., galactosylceramide).Myelin is not The a simple lipid homogeneous composition layer of myelin of proteins sheath and lipids. is distinctive, It also contains made discrete of high and amounts of cholesteroldynamic andlipid enricheddomains in intheglycolipid, external leaflet in of a its ratio plasma of membrane 40%:40%:20% called lipid (cholesterol, rafts [12,13 phospholipid,]. Lipid rafts are characterized by the concentration of selected membrane lipids such as cholesterols, and glycolipid, respectively) compared to most biological membranes (25%:65%:10%) [11]. galactosylceramide, and low levels of phosphatidylcholine. These lipids have roles in myelin Myelinformation is not and a stabilization simple homogeneous [14,15] by includ layering ofand proteins excluding and spec lipids.ific proteins It also into contains particular discrete and dynamiccompartments lipid domains and orchestrating in the external membrane leaflet protein of its trafficking plasma membrane[16,17] and calledsubsequent lipid signal rafts [12,13]. Lipid raftstransduction are characterized [18] (see [16,19 by] for the review). concentration In CNS and of PNS selected myelin, membrane lipid rafts have lipids been such suggested as cholesterols, to galactosylceramide,promote cellular and adhesion low levels by facilitating of phosphatidylcholine. the localization of Thesemembrane lipids and have transmembrane roles in myelin proteins formation and stabilizationmediating axon [14,-15glia] byrecognition including [14,20 and–24 excluding]. specific proteins into particular compartments and orchestrating membrane protein trafficking [16,17] and subsequent signal transduction [18] (see [16,19] for review). In CNS and PNS myelin, lipid rafts have been suggested to promote cellular adhesion by facilitating the localization of membrane and transmembrane proteins mediating axon-glia recognition [14,20–24]. While there are no lipids that are specific to the myelin [25], the three most abundant lipids are (i) cholesterol, (ii) galactosylceramide, and (iii) plasmalogen. Together, these three lipids comprise 65% of the total myelin lipids. Lipid composition
Load more

Recommended publications
  • Bioinformatics Approach for Pattern of Myelin-Specific Proteins And
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Qazvin University of Medical Sciences Repository Biotech Health Sci. 2016 November; 3(4):e38278. doi: 10.17795/bhs-38278. Published online 2016 August 16. Research Article Bioinformatics Approach for Pattern of Myelin-Specific Proteins and Related Human Disorders Samiie Pouragahi,1,2,3 Mohammad Hossein Sanati,4 Mehdi Sadeghi,2 and Marjan Nassiri-Asl3,* 1Department of Molecular Medicine, School of Medicine, Qazvin university of Medical Sciences, Qazvin, IR Iran 2Department of Bioinformatics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, IR Iran 3Department of Pharmacology, Cellular and Molecular Research Center, School of Medicine, Qazvin university of Medical Sciences, Qazvin, IR Iran 4Department of Molecular Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, IR Iran *Corresponding author: Marjan Nassiri-Asl, School of Medicine, Qazvin University of Medical Sciences, Qazvin, IR Iran. Tel: +98-2833336001, Fax: +98-2833324971, E-mail: [email protected] Received 2016 April 06; Revised 2016 May 30; Accepted 2016 June 22. Abstract Background: Recent neuroinformatic studies, on the structure-function interaction of proteins, causative agents basis of human disease have implied that dysfunction or defect of different protein classes could be associated with several related diseases. Objectives: The aim of this study was the use of bioinformatics approaches for understanding the structure, function and relation- ship of myelin protein 2 (PMP2), a myelin-basic protein in the basis of neuronal disorders. Methods: A collection of databases for exploiting classification information systematically, including, protein structure, protein family and classification of human disease, based on a new approach was used.
    [Show full text]
  • Shorthand Notation for Lipid Structures Derived from Mass Spectrometry
    special report Shorthand notation for lipid structures derived from mass spectrometry Gerhard Liebisch , 1, * Juan Antonio Vizcaíno , † Harald Köfeler , ** Martin Trötzmüller , ** William J. Griffi ths , †† Gerd Schmitz , * Friedrich Spener , § , ** and Michael J. O. Wakelam *** Institute of Clinical Chemistry and Laboratory Medicine,* University of Regensburg , Regensburg, Germany ; EMBL-European Bioinformatics Institute , † Hinxton, Cambridge, United Kingdom ; Institute of Molecular Biology and Biochemistry, § and Core Facility Mass Spectrometry,** Medical University of Graz , Graz, Austria ; Institute of Mass Spectrometry, †† College of Medicine, Swansea University , Singleton Park, Swansea, United Kingdom ; and Babraham Institute ,*** Babraham Research Campus, Cambridge, United Kingdom Abstract There is a need for a standardized, practical an- Nomenclature Committee (ILCNC) in 2005 (1 ) and up- notation for structures of lipid species derived from mass dated in 2009 (2 ). This system places lipids into eight cat- spectrometric approaches; i.e., for high-throughput data egories and is available online on the LIPID MAPS website obtained from instruments operating in either high- or low- (http://www.lipidmaps.org). The LIPID MAPS nomencla- Downloaded from resolution modes. This proposal is based on common, ture precisely describes lipid structures. offi cially accepted terms and builds upon the LIPID MAPS terminology. It aims to add defi ned levels of information The key technology for lipid species analysis is mass spec- below the LIPID MAPS nomenclature, as detailed chemical trometry (MS) ( 3, 4 ). Typically, MS analysis without inter- structures, including stereochemistry, are usually not auto- mediate chemical steps does not provide the structural matically provided by mass spectrometric analysis. To this details covered by the LIPID MAPS nomenclature, which www.jlr.org end, rules for lipid species annotation were developed that led mass spectrometrists to use a variety of different nota- refl ect the structural information derived from the analysis.
    [Show full text]
  • Membrane Protein Stabilization Strategies for Structural and Functional Studies
    membranes Review Membrane Protein Stabilization Strategies for Structural and Functional Studies Ekaitz Errasti-Murugarren 1,2,*, Paola Bartoccioni 1,2 and Manuel Palacín 1,2,3,* 1 Laboratory of Amino acid Transporters and Disease, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, 08028 Barcelona, Spain; [email protected] 2 CIBERER (Centro Español en Red de Biomedicina de Enfermedades Raras), 28029 Barcelona, Spain 3 Department of Biochemistry and Molecular Biomedicine, Universitat de Barcelona, 08028 Barcelona, Spain * Correspondence: [email protected] (E.E.-M.); [email protected] (M.P.) Abstract: Accounting for nearly two-thirds of known druggable targets, membrane proteins are highly relevant for cell physiology and pharmacology. In this regard, the structural determination of pharmacologically relevant targets would facilitate the intelligent design of new drugs. The structural biology of membrane proteins is a field experiencing significant growth as a result of the development of new strategies for structure determination. However, membrane protein preparation for structural studies continues to be a limiting step in many cases due to the inherent instability of these molecules in non-native membrane environments. This review describes the approaches that have been developed to improve membrane protein stability. Membrane protein mutagenesis, detergent selection, lipid membrane mimics, antibodies, and ligands are described in this review as approaches to facilitate the production of purified and stable membrane proteins of interest for structural and functional studies. Keywords: membrane proteins; stability; mutagenesis; detergent; lipid; antibody; nanobody; ligand Citation: Errasti-Murugarren, E.; Bartoccioni, P.; Palacín, M. Membrane Protein Stabilization Strategies for Structural and Functional Studies.
    [Show full text]
  • Snapshot: ER-Associated Protein Degradation Pathways Shinichi Kawaguchi and Davis T.W
    SnapShot: ER-Associated Protein Degradation Pathways Shinichi Kawaguchi and Davis T.W. Ng Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, Singapore 117604 1230 Cell 129, June 15, 2007 ©2007 Elsevier Inc. DOI 10.1016/j.cell.2007.06.005 See online version for legend and references. SnapShot: ER-Associated Protein Degradation Pathways Shinichi Kawaguchi and Davis T.W. Ng Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, Singapore 117604 Arrows specify the routes of individual pathways. All pathways culminate in substrate degradation by the 26S proteasome. (Left) ERAD Pathways in Budding Yeast (A) Newly synthesized secretory and membrane proteins enter the ER through the Sec61 protein-conducting channel complex unfolded. Hsp70-related molecular chaperones (Kar2p) bind to nascent polypeptides in the ER lumen and to the cytosolic domains of membrane proteins (Hsp70, B). These factors assist in substrate folding and also assist in their disposal if they fail to fold. Mannose residues on misfolded glycoproteins are trimmed by the ER mannosidase Mns1p (E). Mannose trimming facilitates the recognition of misfolded glycoproteins by luminally oriented lectin factors Htm1p and Yos9p. (C, D, and F) At least two ER membrane-localized E3 ubiquitin ligases organize protein complexes that receive and process misfolded proteins. These complexes define three pathways that recognize lesions in the cytosolic (ERAD-C), transmembrane (ERAD-M), and luminal (ERAD-L) domains of substrates. Both ERAD-M and ERAD-L use the Hrd1 ubiquitin ligase but the luminal factor Yos9p is dispensable for ERAD-M. A Hrd1 complex lacking Yos9p has been observed suggesting dedicated complexes for all three pathways.
    [Show full text]
  • Sphingolipid Metabolism Diseases ⁎ Thomas Kolter, Konrad Sandhoff
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1758 (2006) 2057–2079 www.elsevier.com/locate/bbamem Review Sphingolipid metabolism diseases ⁎ Thomas Kolter, Konrad Sandhoff Kekulé-Institut für Organische Chemie und Biochemie der Universität, Gerhard-Domagk-Str. 1, D-53121 Bonn, Germany Received 23 December 2005; received in revised form 26 April 2006; accepted 23 May 2006 Available online 14 June 2006 Abstract Human diseases caused by alterations in the metabolism of sphingolipids or glycosphingolipids are mainly disorders of the degradation of these compounds. The sphingolipidoses are a group of monogenic inherited diseases caused by defects in the system of lysosomal sphingolipid degradation, with subsequent accumulation of non-degradable storage material in one or more organs. Most sphingolipidoses are associated with high mortality. Both, the ratio of substrate influx into the lysosomes and the reduced degradative capacity can be addressed by therapeutic approaches. In addition to symptomatic treatments, the current strategies for restoration of the reduced substrate degradation within the lysosome are enzyme replacement therapy (ERT), cell-mediated therapy (CMT) including bone marrow transplantation (BMT) and cell-mediated “cross correction”, gene therapy, and enzyme-enhancement therapy with chemical chaperones. The reduction of substrate influx into the lysosomes can be achieved by substrate reduction therapy. Patients suffering from the attenuated form (type 1) of Gaucher disease and from Fabry disease have been successfully treated with ERT. © 2006 Elsevier B.V. All rights reserved. Keywords: Ceramide; Lysosomal storage disease; Saposin; Sphingolipidose Contents 1. Sphingolipid structure, function and biosynthesis ..........................................2058 1.1.
    [Show full text]
  • Supplementary Table 1. Down-Regulation of Oligodendrocyte Genes in Schizophrenia
    Supplementary Table 1. Down-regulation of oligodendrocyte genes in schizophrenia Schizophrenia ID Accession Symbol product fold change P value oligodendrocyte transcription factors 36018_at AJ001183 SOX10 SRY (sex determining region Y)-box 10 -1.60 0.001 40624_at U48250 OLIG2 oligodendrocyte lineage transcription factor 2 -1.30 0.019 32187_at AB028973 MYT1 myelin transcription factor 1 1.12 0.571 33539_at W28567 MYEF2 myelin expression factor 2 -1.04 0.887 oligodendrocyte-expressed genes 38558_at M29273 MAG myelin associated glycoprotein -1.76 0.004 41158_at M54927 PLP1 proteolipid protein 1 -1.50 0.011 38499_s_at D28113 MOBP myelin-associated oligodendrocyte basic protein -1.59 0.017 35903_at M63623 OMG oligodendrocyte myelin glycoprotein -1.15 0.022 38653_at D11428 PMP22 peripheral myelin protein 22 -1.28 0.058 38051_at X76220 MAL mal, T-cell differentiation protein -1.11 0.065 612_s_at M19650 CNP 2',3'-cyclic nucleotide 3' phosphodiesterase -1.17 0.072 32538_at S95936 TF transferrin -1.48 0.098 32612_at X04412 GSN gelsolin (amyloidosis, Finnish type) -1.23 0.118 39598_at X04325 GJB1 gap junction protein, beta 1, 32kDa -1.10 0.416 37867_at Z48051 MOG myelin oligodendrocyte glycoprotein 1.39 0.600 35328_at AF055023 NF1 neurofibromin 1 -1.03 0.973 35817_at M13577 MBP myelin basic protein 1.02 1 other oligodendrocyte-related genes 41346_at AJ007583 LARGE like-glycosyltransferase -1.02 0.786 32719_at L41827 NRG1 neuregulin 1 1.07 0.792 1585_at M34309 ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 -1.10 0.294 40387_at U80811
    [Show full text]
  • Attenuation of Ganglioside GM1 Accumulation in the Brain of GM1 Gangliosidosis Mice by Neonatal Intravenous Gene Transfer
    Gene Therapy (2003) 10, 1487–1493 & 2003 Nature Publishing Group All rights reserved 0969-7128/03 $25.00 www.nature.com/gt RESEARCH ARTICLE Attenuation of ganglioside GM1 accumulation in the brain of GM1 gangliosidosis mice by neonatal intravenous gene transfer N Takaura1, T Yagi2, M Maeda2, E Nanba3, A Oshima4, Y Suzuki5, T Yamano1 and A Tanaka1 1Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan; 2Department of Neurobiology and Anatomy, Osaka City University Graduate School of Medicine, Osaka, Japan; 3Gene Research Center, Tottori University, Yonago, Japan; 4Department of Pediatrics, Takagi Hospital, Saitama, Japan; and 5Pediatrics, Clinical Research Center, Nasu Institute for Developmental Disabilities, International University of Health and Welfare, Ohtawara, Japan A single intravenous injection with 4 Â 107 PFU of recombi- ganglioside GM1 was above the normal range in all treated nant adenovirus encoding mouse b-galactosidase cDNA to mice, which was speculated to be the result of reaccumula- newborn mice provided widespread increases of b-galacto- tion. However, the values were still definitely lower in most of sidase activity, and attenuated the development of the the treated mice than those in untreated mice. In the disease including the brain at least for 60 days. The b- histopathological study, X-gal-positive cells, which showed galactosidase activity showed 2–4 times as high a normal the expression of exogenous b-galactosidase gene, were activity in the liver and lung, and 50 times in the heart. In the observed in the brain. It is noteworthy that neonatal brain, while the activity was only 10–20% of normal, the administration via blood vessels provided access to the efficacy of the treatment was distinct.
    [Show full text]
  • Nervous Tissue
    Nervous Tissue • Controls and integrates all body activities within limits that maintain life • Three basic functions – sensing changes with sensory receptors • fullness of stomach or sun on your face – interpreting and remembering those changes – reacting to those changes with effectors • muscular contractions • glandular secretions Major Structures of the Nervous System • Brain, cranial nerves, spinal cord, spinal nerves, ganglia, enteric plexuses and sensory receptors Organization of the Nervous System • CNS is brain and spinal cord • PNS is everything else Nervous System Divisions • Central nervous system (CNS) – consists of the brain and spinal cord • Peripheral nervous system (PNS) – consists of cranial and spinal nerves that contain both sensory and motor fibers – connects CNS to muscles, glands & all sensory receptors Subdivisions of the PNS • Somatic (voluntary) nervous system (SNS) – neurons from cutaneous and special sensory receptors to the CNS – motor neurons to skeletal muscle tissue • Autonomic (involuntary) nervous systems – sensory neurons from visceral organs to CNS – motor neurons to smooth & cardiac muscle and glands • sympathetic division (speeds up heart rate) • parasympathetic division (slow down heart rate) • Enteric nervous system (ENS) – involuntary sensory & motor neurons control GI tract – neurons function independently of ANS & CNS Neurons • Functional unit of nervous system • Have capacity to produce action potentials – electrical excitability • Cell body – single nucleus with prominent nucleolus – Nissl
    [Show full text]
  • Oligodendrocytes in Development, Myelin Generation and Beyond
    cells Review Oligodendrocytes in Development, Myelin Generation and Beyond Sarah Kuhn y, Laura Gritti y, Daniel Crooks and Yvonne Dombrowski * Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, UK; [email protected] (S.K.); [email protected] (L.G.); [email protected] (D.C.) * Correspondence: [email protected]; Tel.: +0044-28-9097-6127 These authors contributed equally. y Received: 15 October 2019; Accepted: 7 November 2019; Published: 12 November 2019 Abstract: Oligodendrocytes are the myelinating cells of the central nervous system (CNS) that are generated from oligodendrocyte progenitor cells (OPC). OPC are distributed throughout the CNS and represent a pool of migratory and proliferative adult progenitor cells that can differentiate into oligodendrocytes. The central function of oligodendrocytes is to generate myelin, which is an extended membrane from the cell that wraps tightly around axons. Due to this energy consuming process and the associated high metabolic turnover oligodendrocytes are vulnerable to cytotoxic and excitotoxic factors. Oligodendrocyte pathology is therefore evident in a range of disorders including multiple sclerosis, schizophrenia and Alzheimer’s disease. Deceased oligodendrocytes can be replenished from the adult OPC pool and lost myelin can be regenerated during remyelination, which can prevent axonal degeneration and can restore function. Cell population studies have recently identified novel immunomodulatory functions of oligodendrocytes, the implications of which, e.g., for diseases with primary oligodendrocyte pathology, are not yet clear. Here, we review the journey of oligodendrocytes from the embryonic stage to their role in homeostasis and their fate in disease. We will also discuss the most common models used to study oligodendrocytes and describe newly discovered functions of oligodendrocytes.
    [Show full text]
  • Predicting Protein-Membrane Interfaces of Peripheral Membrane
    bioRxiv preprint doi: https://doi.org/10.1101/2021.06.28.450157; this version posted June 29, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Predicting protein-membrane interfaces of pe- ripheral membrane proteins using ensemble machine learning Alexios Chatzigoulas1,2,* and Zoe Cournia1,* 1Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou, 11527 Athens, Greece, 2Depart- ment of Informatics and Telecommunications, National and Kapodistrian University of Athens, 15784 Athens, Greece *To whom correspondence should be addressed. Abstract Motivation: Abnormal protein-membrane attachment is involved in deregulated cellular pathways and in disease. Therefore, the possibility to modulate protein-membrane interactions represents a new promising therapeutic strategy for peripheral membrane proteins that have been considered so far undruggable. A major obstacle in this drug design strategy is that the membrane binding domains of peripheral membrane proteins are usually not known. The development of fast and efficient algorithms predicting the protein-membrane interface would shed light into the accessibility of membrane-protein interfaces by drug-like molecules. Results: Herein, we describe an ensemble machine learning methodology and algorithm for predicting membrane-penetrating residues. We utilize available experimental data in the literature for training 21 machine learning classifiers and a voting classifier. Evaluation of the ensemble classifier accuracy pro- duced a macro-averaged F1 score = 0.92 and an MCC = 0.84 for predicting correctly membrane-pen- etrating residues on unknown proteins of an independent test set.
    [Show full text]
  • Chapter 8 Nervous System
    Chapter 8 Nervous System I. Functions A. Sensory Input – stimuli interpreted as touch, taste, temperature, smell, sound, blood pressure, and body position. B. Integration – CNS processes sensory input and initiates responses categorizing into immediate response, memory, or ignore C. Homeostasis – maintains through sensory input and integration by stimulating or inhibiting other systems D. Mental Activity – consciousness, memory, thinking E. Control of Muscles & Glands – controls skeletal muscle and helps control/regulate smooth muscle, cardiac muscle, and glands II. Divisions of the Nervous system – 2 anatomical/main divisions A. CNS (Central Nervous System) – consists of the brain and spinal cord B. PNS (Peripheral Nervous System) – consists of ganglia and nerves outside the brain and spinal cord – has 2 subdivisions 1. Sensory Division (Afferent) – conducts action potentials from PNS toward the CNS (by way of the sensory neurons) for evaluation 2. Motor Division (Efferent) – conducts action potentials from CNS toward the PNS (by way of the motor neurons) creating a response from an effector organ – has 2 subdivisions a. Somatic Motor System – controls skeletal muscle only b. Autonomic System – controls/effects smooth muscle, cardiac muscle, and glands – 2 branches • Sympathetic – accelerator “fight or flight” • Parasympathetic – brake “resting and digesting” * 4 Types of Effector Organs: skeletal muscle, smooth muscle, cardiac muscle, and glands. III. Cells of the Nervous System A. Neurons – receive stimuli and transmit action potentials
    [Show full text]
  • Improvement of Spontaneous Alternation Behavior Deficit by Activation Ofα4β2 Nicotinic Acetylcholine Receptor Signaling in the Ganglioside GM3-Deficient Mice
    Biomedical Research 34 (4) 189-195, 2013 Improvement of spontaneous alternation behavior deficit by activation of α4β2 nicotinic acetylcholine receptor signaling in the ganglioside GM3- deficient mice 1 1 2 1 2 1 Kimie NIIMI , Chieko NISHIOKA , Tomomi MIYAMOTO , Eiki TAKAHASHI , Ichiro MIYOSHI , Chitoshi ITAKURA , 3, 4 and Tadashi YAMASHITA 1 Riken Brain Science Institute, Saitama 351-0198, Japan; 2 Graduate School of Medical Sciences, Nagoya City University, Nagoya 467- 8601, Japan; 3 Graduate School of Veterinary Medicine, Azabu University, Sagamihara 252-5201, Japan; and 4 World Class University Program, Kyungpook National University School of Medicine, Daegu, South Korea (Received 13 May 2013; and accepted 17 June 2013) ABSTRACT We have reported that in ganglioside GM3-deficient (GM3−/−) mice, spontaneous alternation be- havior assessed by a Y-maze task was significantly lower, and total arm entries were significantly higher than in wild-type mice. The objective of the present study was to examine the role of nico- tinic acetylcholine receptor (nAChR) signaling in impairment of spontaneous alternation behavior of GM3−/− mice. Nicotine treatment (0.3, 1.0 mg/kg, s.c.) dose dependently improved the sponta- neous alternation deficit without affecting total arm entries in GM3−/− mice. The nicotine-induced (1.0 mg/kg, s.c.) improvement was significantly abolished by the nAChR antagonist mecamyla- mine (1.0 mg/kg, i.p.). The α4β2 nAChR antagonist dihydro-β-erythroidine (2.5, 10.0 mg/kg, i.p.) dose dependently counteracted the nicotine-induced improvement of spontaneous alternation in GM3−/− mice, whereas the α7 nAChR antagonist methyllycaconitine (2.5, 10.0 mg/kg, i.p.) did not.
    [Show full text]