Multiple Sclerosis: Lipids, Lymphocytes, and Vitamin D

Immunometabolism
C E Hayes, James M Ntambi

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. We review the two core MS features, myelin instability, fragmentation, and remyelination failure, and dominance of pathogenic CD4+ Th17 cells over protective CD4+ Treg cells. To better understand myelin pathology, we describe myelin biosynthesis, structure, and function, then highlight stearoyl-CoA desaturase (SCD) in nervonic acid biosynthesis and nervonic acid's contribution to myelin stability. Noting that vitamin D deficiency decreases SCD in the periphery, we propose it also decreases SCD in oligodendrocytes, disrupting the nervonic acid supply and causing myelin instability and fragmentation. To better understand the distorted Th17/Treg cell balance, we summarize Th17 cell contributions to MS pathogenesis, then highlight how 1,25-dihydroxyvitamin D3 signaling from microglia to CD4+ T cells restores Treg cell dominance. This signaling rapidly increases flux through the methionine cycle, removing homocysteine, replenishing S-adenosyl-methionine, and improving epigenetic marking. Noting that DNA hypomethylation and inappropriate DRB1*1501 expression were observed in MS patient CD4+ T cells, we propose that vitamin D deficiency thw...Continue Reading

References

Aug 1, 1986·The Journal of Clinical Investigation·D D BikleP Elias
Sep 1, 1987·The Journal of Pediatrics·P DuquetteW Hader
Jan 1, 1972·Zeitschrift für Neurologie·B GerstlJ K Smith
Sep 16, 1983·Science·D M ProvvediniS C Manolagas
Jul 1, 1994·Brain Research. Molecular Brain Research·I NeveuP Brachet
Apr 1, 1994·Medical Hypotheses·J R SargentR Wilson
Sep 5, 1996·Brain Research. Molecular Brain Research·P NaveilhanM Metsis
Apr 1, 1997·Neurochemical Research·J N LaroccaW T Norton
Dec 1, 1998·Journal of Neurochemistry·M Martínez, I Mougan
Sep 1, 2000·The American Journal of Clinical Nutrition·J WortsmanM F Holick
Dec 1, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·R FaggioniC Grunfeld
Jan 10, 2003·Journal of Cellular Biochemistry·Michael F Holick
Dec 12, 2003·American Journal of Human Genetics·Jorge R OksenbergStephen L Hauser
Dec 23, 2003·Journal of Neuroscience Research·F D TestaiG Dawson
Jul 23, 2004·The Journal of Biological Chemistry·Suzanne E WahrleDavid M Holtzman
Dec 14, 2004·Journal of Chemical Neuroanatomy·Darryl W EylesJohn J McGrath
Jun 3, 2005·Human Molecular Genetics·David A DymentGeorge C Ebers
Aug 17, 2005·Progress in Neuro-psychopharmacology & Biological Psychiatry·Perminder S Sachdev
Aug 19, 2005·Journal of Neurology, Neurosurgery, and Psychiatry·D M WingerchukG C Ebers
Sep 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karen M Spach, Colleen E Hayes
Dec 15, 2005·The Journal of Biological Chemistry·Barbara KartenJean E Vance
Jan 20, 2006·Journal of Neurology, Neurosurgery, and Psychiatry·G S M RamsaransingJ De Keyser
Apr 21, 2006·American Journal of Physiology. Cell Physiology·Seema Tiwari-WoodruffJeff Bronstein
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karen M SpachColleen E Hayes
Sep 12, 2007·PLoS Genetics·Sreeram V RamagopalanGeorge C Ebers
Sep 21, 2007·Multiple Sclerosis : Clinical and Laboratory Research·S SahinS Karsidag
Nov 22, 2007·The Journal of Nutrition·Matthew J RowlingJames C Fleet
Dec 18, 2007·Journal of Neurology·C RussoUmberto Aguglia
Dec 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·G C DeLucaG C Ebers
Jan 4, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·John D CahoyBen A Barres
Mar 4, 2008·Molecular and Cellular Endocrinology·Paul H AndersonHoward A Morris

❮ Previous
Next ❯

Citations

Jan 5, 2021·Frontiers in Immunology·Gunnar HouenJette Lautrup Frederiksen
Nov 5, 2020·Nutrients·Joseph MercolaCarol L Wagner
Nov 20, 2020·International Journal of Molecular Sciences·Lucas M O'NeillJames M Ntambi
Feb 18, 2021·Multiple Sclerosis and Related Disorders·Gavin GiovannoniDaniela Pohl

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping
imaging techniques

Software Mentioned

Helios

Related Concepts

Related Feeds

Related Papers

Journal of Molecular Neuroscience : MN
Mina AbdolahiAli Akbar Saboor-Yaraghi
Current Medicinal Chemistry
Masaaki NiinoHidenao Sasaki
Proceedings of the National Academy of Sciences of the United States of America
Manuel ZeitelhoferMaja Jagodic
© 2022 Meta ULC. All rights reserved