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Association of a Marker of N-Acetylglucosamine With Progressive Multiple Sclerosis and Neurodegeneration

Educational Objective
To determine whether serum concentration of N-acetylglucosamine (GlcNAc) is altered in patients with multiple sclerosis.
1 Credit CME
Key Points

Question  Is the serum concentration of N-acetylglucosamine (GlcNAc) altered in patients with multiple sclerosis?

Findings  This cross-sectional study found that patients with a progressive multiple sclerosis subtype and more severe disease have reduced serum levels of a marker of GlcNAc. In addition, GlcNAc is a rate-limiting substrate for N-glycan branching, which has been shown to regulate immunoactivity and myelination.

Meaning  This study suggests that GlcNAc and N-glycan branching are associated with multiple sclerosis in general and progressive multiple sclerosis in particular.


Importance  N-glycan branching modulates cell surface receptor availability, and its deficiency in mice promotes inflammatory demyelination, reduced myelination, and neurodegeneration. N-acetylglucosamine (GlcNAc) is a rate-limiting substrate for N-glycan branching, but, to our knowledge, endogenous serum levels in patients with multiple sclerosis (MS) are unknown.

Objective  To investigate a marker of endogenous serum GlcNAc levels in patients with MS.

Design, Setting, and Participants  A cross-sectional discovery study and cross-sectional confirmatory study were conducted at 2 academic MS centers in the US and Germany. The discovery study recruited 54 patients with MS from an outpatient clinic as well as 66 healthy controls between April 20, 2010, and June 21, 2013. The confirmatory study recruited 180 patients with MS from screening visits at an academic MS study center between April 9, 2007, and February 29, 2016. Serum samples were analyzed from December 2, 2013, to March 2, 2015. Statistical analysis was performed from February 23, 2020, to March 18, 2021.

Main Outcomes and Measures  Serum levels of GlcNAc plus its stereoisomers, termed N-acetylhexosamine (HexNAc), were assessed using targeted tandem mass spectroscopy. Secondary outcomes (confirmatory study) comprised imaging and clinical disease markers.

Results  The discovery cohort included 66 healthy controls (38 women; mean [SD] age, 42 [20] years), 33 patients with relapsing-remitting MS (RRMS; 25 women; mean [SD] age, 50 [11] years), and 21 patients with progressive MS (PMS; 14 women; mean [SD] age, 55 [7] years). The confirmatory cohort included 125 patients with RRMS (83 women; mean [SD] age, 40 [9] years) and 55 patients with PMS (22 women; mean [SD] age, 49 [80] years). In the discovery cohort, the mean (SD) serum level of GlcNAc plus its stereoisomers (HexNAc) was 710 (174) nM in healthy controls and marginally reduced in patients with RRMS (mean [SD] level, 682 [173] nM; P = .04), whereas patients with PMS displayed markedly reduced levels compared with healthy controls (mean [SD] level, 548 [101] nM; P = 9.55 × 10−9) and patients with RRMS (P = 1.83 × 10−4). The difference between patients with RRMS (mean [SD] level, 709 [193] nM) and those with PMS (mean [SD] level, 405 [161] nM; P = 7.6 × 10−18) was confirmed in the independent confirmatory cohort. Lower HexNAc serum levels correlated with worse expanded disability status scale scores (ρ = –0.485; P = 4.73 × 10−12), lower thalamic volume (t = 1.7; P = .04), and thinner retinal nerve fiber layer (B = 0.012 [SE = 7.5 × 10−11]; P = .008). Low baseline serum HexNAc levels correlated with a greater percentage of brain volume loss at 18 months (t = 1.8; P = .04).

Conclusions and Relevance  This study suggests that deficiency of GlcNAc plus its stereoisomers (HexNAc) may be a biomarker for PMS. Previous preclinical, human genetic, and ex vivo human mechanistic studies revealed that N-glycan branching and/or GlcNAc may reduce proinflammatory responses, promote myelin repair, and decrease neurodegeneration. Combined, the data suggest that GlcNAc deficiency may be associated with progressive disease and neurodegeneration in patients with MS.

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Article Information

Accepted for Publication: March 11, 2021.

Published Online: May 10, 2021. doi:10.1001/jamaneurol.2021.1116

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Brandt AU et al. JAMA Neurology.

Corresponding Author: Michael Demetriou, MD, PhD, Department of Neurology, University of California, Irvine, 208 Sprague Hall, Irvine, CA 92697 (mdemetriou@uci.edu).

Author Contributions: Drs Brandt and Demetriou had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Brandt, Sy, Dennis, Paul, Demetriou.

Acquisition, analysis, or interpretation of data: Brandt, Bellmann-Strobl, Newton, Pawling, Zimmermann, Yu, Chien, Dörr, Wuerfel, Dennis, Paul, Demetriou.

Drafting of the manuscript: Brandt, Sy, Yu, Chien, Demetriou.

Critical revision of the manuscript for important intellectual content: Sy, Bellmann-Strobl, Newton, Pawling, Zimmermann, Chien, Dörr, Wuerfel, Dennis, Paul, Demetriou.

Statistical analysis: Brandt, Yu.

Obtained funding: Brandt, Paul, Demetriou.

Administrative, technical, or material support: Bellmann-Strobl, Newton, Zimmermann, Chien, Dörr, Wuerfel, Dennis, Paul.

Supervision: Brandt, Sy, Wuerfel, Dennis, Paul, Demetriou.

Conflict of Interest Disclosures: Dr Brandt reported receiving grants and personal fees from Guthy Jackson Foundation, Einstein Foundation, BMB, and Deutsche Forschungsgemeinschaft Exc 157 during the conduct of the study; being cofounder and receiving shares from Motognosis GmbH and Nocturne GmbH outside the submitted work; and having a patent for GlcNAc as Serum Biomarker for Multiple Sclerosis issued. Dr Sy reported having an ownership stake in Glixis Therapeutics LLC outside the submitted work. Dr Bellmann-Strobl reported receiving nonfinancial support from Biogen Idec; personal fees from Bayer Healthcare, Merck Serono, Teva Pharmaceuticals, Roche, and Novartis; and personal fees and nonfinancial support from Sanofi Genzyme outside the submitted work. Dr Zimmermann reported receiving grants from Novartis and personal fees from Bayer Healthcare outside the submitted work. Ms Chien reported receiving speaking fees from Bayer and research funding from Novartis unrelated to this study. Dr Dörr reported receiving grants from Bayer during the conduct of the study; and personal fees from Bayer, Biogen, Novartis, Roche, Merck Serono, Sanofi, and Teva outside the submitted work. Dr Wuerfel reported receiving grants from the EU (Horizon2020) and the Swiss National Science Foundation; and serving on advisory boards for Actelion, Genzyme-Sanofi, Idorsia, InmuneBio, Novartis, and Roche. Dr Dennis reported holding a patent pending for PCT/US16/15807 N-Acetyl Glucosamine as a Biomarker of MS Disease Course and being an inventor on this patent, a patent on methods and compositions for preventing and treating a disease related to glycan dysregulation issued to Wellsley Therapeutics, and a patent on Analogs of N-acetylglucosamine pending; and being a cofounder of and holding shares in Glixis Therapeutics LLC. Dr Paul reported receiving grants from Celgene, Novartis, BMBF, Alexion, Guthy Jackson Foundation, Falck-Foundation, Roche, Almirall, Deutsche Forschungsgemeinschaft, Einstein Foundation, Biogen, and Merck Serono; research support and personal fees from UCB, Roche, Alexion, Sanofi Genzyme, Mitsubishi Tanabe, Bayer, Merck Serono, and Viela Bio outside the submitted work. Dr Demetriou reported receiving grants from the National Institute of Allergy and Infectious Disease and the National Center for Complementary and Integrative Health during the conduct of the study; having a patent for US9775859B2 issued, a patent for US10495646B2 issued, and a patent pending for US20170042919A1; and being a cofounder and shareholder of Glixis Therapeutics. No other disclosures were reported.

Funding/Support: The UC Irvine discovery cohort was supported by grant R01AI108917 from the National Institute of Allergy and Infectious Disease and grant R01AT007452 from the National Center for Complementary and Integrative Health (Dr Demetriou). The confirmation cohort study was supported by DFG grant Exc. 257 (Dr Paul).

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank Cynthia Kraut, Technical Radiology Assistant, Charité–Universitätsmedizin Berlin, and Susan Pikol, Technical Radiology Assistant, Charité–Universitätsmedizin Berlin, for MRI assistance and Bibiane Seeger, Laboratory Assistant, Charité–Universitätsmedizin Berlin, and Carey F. Li, PhD, University of California, Irvine, for laboratory assistance. They were all compensated for their work as employees of their respective institutions. We thank Claudia Kawas, for access to participants from the 90+ Cohort.

Reich  DS , Lucchinetti  CF , Calabresi  PA .  Multiple sclerosis.   N Engl J Med. 2018;378(2):169-180. doi:10.1056/NEJMra1401483 PubMedGoogle ScholarCrossref
Weinshenker  BG , Bass  B , Rice  GP ,  et al.  The natural history of multiple sclerosis: a geographically based study, I: clinical course and disability.   Brain. 1989;112(pt 1):133-146. doi:10.1093/brain/112.1.133 PubMedGoogle ScholarCrossref
Cree  BAC , Hollenbach  JA , Bove  R ,  et al; University of California, San Francisco MS-EPIC Team.  Silent progression in disease activity–free relapsing multiple sclerosis.   Ann Neurol. 2019;85(5):653-666. doi:10.1002/ana.25463 PubMedGoogle ScholarCrossref
Demetriou  M , Granovsky  M , Quaggin  S , Dennis  JW .  Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation.   Nature. 2001;409(6821):733-739. doi:10.1038/35055582 PubMedGoogle ScholarCrossref
Partridge  EA , Le Roy  C , Di Guglielmo  GM ,  et al.  Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis.   Science. 2004;306(5693):120-124. doi:10.1126/science.1102109 PubMedGoogle ScholarCrossref
Lau  KS , Partridge  EA , Grigorian  A ,  et al.  Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation.   Cell. 2007;129(1):123-134. doi:10.1016/j.cell.2007.01.049 PubMedGoogle ScholarCrossref
Dennis  JW , Nabi  IR , Demetriou  M .  Metabolism, cell surface organization, and disease.   Cell. 2009;139(7):1229-1241. doi:10.1016/j.cell.2009.12.008 PubMedGoogle ScholarCrossref
Chen  IJ , Chen  HL , Demetriou  M .  Lateral compartmentalization of T cell receptor versus CD45 by galectin-N-glycan binding and microfilaments coordinate basal and activation signaling.   J Biol Chem. 2007;282(48):35361-35372. doi:10.1074/jbc.M706923200 PubMedGoogle ScholarCrossref
Zhou  RW , Mkhikian  H , Grigorian  A ,  et al.  N-glycosylation bidirectionally extends the boundaries of thymocyte positive selection by decoupling Lck from Ca2+ signaling.   Nat Immunol. 2014;15(11):1038-1045. doi:10.1038/ni.3007 PubMedGoogle ScholarCrossref
Mkhikian  H , Mortales  CL , Zhou  RW ,  et al.  Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis.   Elife. 2016;5:5. doi:10.7554/eLife.14814 PubMedGoogle ScholarCrossref
Araujo  L , Khim  P , Mkhikian  H , Mortales  CL , Demetriou  M .  Glycolysis and glutaminolysis cooperatively control T cell function by limiting metabolite supply to N-glycosylation.   Elife. 2017;6:6. doi:10.7554/eLife.21330 PubMedGoogle ScholarCrossref
Mortales  CL , Lee  SU , Demetriou  M .  N-glycan branching is required for development of mature B cells.   J Immunol. 2020;205(3):630-636. doi:10.4049/jimmunol.2000101 PubMedGoogle ScholarCrossref
Mortales  CL , Lee  SU , Manousadjian  A , Hayama  KL , Demetriou  M .  N-glycan branching decouples B cell innate and adaptive immunity to control inflammatory demyelination.   iScience. 2020;23(8):101380. doi:10.1016/j.isci.2020.101380 PubMedGoogle Scholar
Grigorian  A , Demetriou  M .  Manipulating cell surface glycoproteins by targeting N-glycan–galectin interactions.   Methods Enzymol. 2010;480:245-266. doi:10.1016/S0076-6879(10)80012-6 PubMedGoogle ScholarCrossref
Grigorian  A , Araujo  L , Naidu  NN , Place  DJ , Choudhury  B , Demetriou  M .  N-acetylglucosamine inhibits T-helper 1 (Th1)/T-helper 17 (Th17) cell responses and treats experimental autoimmune encephalomyelitis.   J Biol Chem. 2011;286(46):40133-40141. doi:10.1074/jbc.M111.277814 PubMedGoogle ScholarCrossref
Grigorian  A , Lee  SU , Tian  W ,  et al.  Control of T cell-mediated autoimmunity by metabolite flux to N-glycan biosynthesis.   J Biol Chem. 2007;282(27):20027-20035. doi:10.1074/jbc.M701890200 PubMedGoogle ScholarCrossref
Lee  SU , Grigorian  A , Pawling  J ,  et al.  N-glycan processing deficiency promotes spontaneous inflammatory demyelination and neurodegeneration.   J Biol Chem. 2007;282(46):33725-33734. doi:10.1074/jbc.M704839200 PubMedGoogle ScholarCrossref
Grigorian  A , Demetriou  M .  Mgat5 deficiency in T cells and experimental autoimmune encephalomyelitis.   ISRN Neurol. 2011;2011:374314. doi:10.5402/2011/374314 PubMedGoogle Scholar
Sy  M , Brandt  AU , Lee  SU ,  et al.  N-acetylglucosamine drives myelination by triggering oligodendrocyte precursor cell differentiation.   J Biol Chem. 2020;295(51):17413-17424. doi:10.1074/jbc.RA120.015595 PubMedGoogle ScholarCrossref
Mkhikian  H , Grigorian  A , Li  CF ,  et al.  Genetics and the environment converge to dysregulate N-glycosylation in multiple sclerosis.   Nat Commun. 2011;2:334. doi:10.1038/ncomms1333 PubMedGoogle ScholarCrossref
Li  CF , Zhou  RW , Mkhikian  H , Newton  BL , Yu  Z , Demetriou  M .  Hypomorphic MGAT5 polymorphisms promote multiple sclerosis cooperatively with MGAT1 and interleukin-2 and 7 receptor variants.   J Neuroimmunol. 2013;256(1-2):71-76. doi:10.1016/j.jneuroim.2012.12.008 PubMedGoogle ScholarCrossref
Brynedal  B , Wojcik  J , Esposito  F ,  et al.  MGAT5 alters the severity of multiple sclerosis.   J Neuroimmunol. 2010;220(1-2):120-124. doi:10.1016/j.jneuroim.2010.01.003 PubMedGoogle ScholarCrossref
Bäcker-Koduah  P , Infante-Duarte  C , Ivaldi  F ,  et al.  Effect of vitamin D supplementation on N-glycan branching and cellular immunophenotypes in MS.   Ann Clin Transl Neurol. 2020;7(9):1628-1641. doi:10.1002/acn3.51148 PubMedGoogle ScholarCrossref
Ye  Z , Marth  JD .  N-glycan branching requirement in neuronal and postnatal viability.   Glycobiology. 2004;14(6):547-558. doi:10.1093/glycob/cwh069 PubMedGoogle ScholarCrossref
Ryczko  MC , Pawling  J , Chen  R ,  et al.  Metabolic reprogramming by hexosamine biosynthetic and Golgi N-glycan branching pathways.   Sci Rep. 2016;6(1):23043-23043. doi:10.1038/srep23043 PubMedGoogle ScholarCrossref
Sassi  A , Lazaroski  S , Wu  G ,  et al.  Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels.   J Allergy Clin Immunol. 2014;133(5):1410-1419, 1419.e1-1419.e13. doi:10.1016/j.jaci.2014.02.025PubMedGoogle ScholarCrossref
Zhang  Y , Yu  X , Ichikawa  M ,  et al.  Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment.   J Allergy Clin Immunol. 2014;133(5):1400-1409, 1409.e1-1409.e5. doi:10.1016/j.jaci.2014.02.013PubMedGoogle ScholarCrossref
Polman  CH , Reingold  SC , Banwell  B ,  et al.  Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria.   Ann Neurol. 2011;69(2):292-302. doi:10.1002/ana.22366 PubMedGoogle ScholarCrossref
Lublin  FD , Reingold  SC ; National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis.  Defining the clinical course of multiple sclerosis: results of an international survey.   Neurology. 1996;46(4):907-911. doi:10.1212/WNL.46.4.907 PubMedGoogle ScholarCrossref
Polman  CH , Reingold  SC , Edan  G ,  et al.  Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald criteria”.   Ann Neurol. 2005;58(6):840-846. doi:10.1002/ana.20703 PubMedGoogle ScholarCrossref
Kurtzke  JF .  Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS).   Neurology. 1983;33(11):1444-1452. doi:10.1212/WNL.33.11.1444 PubMedGoogle ScholarCrossref
Cutter GR, Baier ML, Rudick RA, et al. Development of a multiple sclerosis functional composite as a clinical trial outcome measure.  Brain. 1999;122(pt 5):871-882.
National Multiple Sclerosis Society. Multiple Sclerosis Functional Composite (MSFC) administration and scoring manual. Revised October 2001. Accessed April 6, 2021. http://main.nationalmssociety.org/docs/HOM/MSFC_Manual_and_Forms.pdf
Roxburgh RHSR, Seaman SR, Masterman T, et al. Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity.  Neurology. 2005;64(7):1144-1151.
Patenaude B, Smith SM, Kennedy DN, Jenkinson M. A bayesian model of shape and appearance for subcortical brain segmentation.  Neuroimage. 2011;56(3):907-922.
Smith SM, Zhang Y, Jenkinson M, et al. Accurate, robust, and automated longitudinal and cross-sectional brain change analysis.  Neuroimage. 2002;17(1):479-489.
De Stefano  N , Stromillo  ML , Giorgio  A ,  et al.  Establishing pathological cut-offs of brain atrophy rates in multiple sclerosis.   J Neurol Neurosurg Psychiatry. 2016;87(1):93-99.PubMedGoogle Scholar
Dörr J, Wernecke KD, Bock M, et al. Association of retinal and macular damage with brain atrophy in multiple sclerosis.  PLoS One. 2011;6(4):e18132.
Abdel Rahman  AM , Ryczko  M , Pawling  J , Dennis  JW .  Probing the hexosamine biosynthetic pathway in human tumor cells by multitargeted tandem mass spectrometry.   ACS Chem Biol. 2013;8(9):2053-2062. doi:10.1021/cb4004173 PubMedGoogle ScholarCrossref
Henry  RG , Shieh  M , Okuda  DT , Evangelista  A , Gorno-Tempini  ML , Pelletier  D .  Regional grey matter atrophy in clinically isolated syndromes at presentation.   J Neurol Neurosurg Psychiatry. 2008;79(11):1236-1244. doi:10.1136/jnnp.2007.134825 PubMedGoogle ScholarCrossref
Kanamori  A , Escano  MF , Eno  A ,  et al.  Evaluation of the effect of aging on retinal nerve fiber layer thickness measured by optical coherence tomography.   Ophthalmologica. 2003;217(4):273-278. doi:10.1159/000070634 PubMedGoogle ScholarCrossref
McGinley  MP , Goldschmidt  CH , Rae-Grant  AD .  Diagnosis and treatment of multiple sclerosis: a review.   JAMA. 2021;325(8):765-779. doi:10.1001/jama.2020.26858 PubMedGoogle ScholarCrossref
Feinstein  A , Freeman  J , Lo  AC .  Treatment of progressive multiple sclerosis: what works, what does not, and what is needed.   Lancet Neurol. 2015;14(2):194-207. doi:10.1016/S1474-4422(14)70231-5 PubMedGoogle ScholarCrossref
Coetzee  T , Zaratin  P , Gleason  TL .  Overcoming barriers in progressive multiple sclerosis research.   Lancet Neurol. 2015;14(2):132-133. doi:10.1016/S1474-4422(14)70323-0 PubMedGoogle ScholarCrossref
Mahad  DH , Trapp  BD , Lassmann  H .  Pathological mechanisms in progressive multiple sclerosis.   Lancet Neurol. 2015;14(2):183-193. doi:10.1016/S1474-4422(14)70256-X PubMedGoogle ScholarCrossref
Montalban  X , Hauser  SL , Kappos  L ,  et al; ORATORIO Clinical Investigators.  Ocrelizumab versus placebo in primary progressive multiple sclerosis.   N Engl J Med. 2017;376(3):209-220. doi:10.1056/NEJMoa1606468 PubMedGoogle ScholarCrossref
Kappos  L , Bar-Or  A , Cree  BAC ,  et al; EXPAND Clinical Investigators.  Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study.   Lancet. 2018;391(10127):1263-1273. doi:10.1016/S0140-6736(18)30475-6 PubMedGoogle ScholarCrossref
Villoslada  P , Steinman  L .  New targets and therapeutics for neuroprotection, remyelination and repair in multiple sclerosis.   Expert Opin Investig Drugs. 2020;29(5):443-459. doi:10.1080/13543784.2020.1757647 PubMedGoogle ScholarCrossref
Filippi  M , Preziosa  P , Barkhof  F ,  et al.  Diagnosis of progressive multiple sclerosis from the imaging perspective: a review.   JAMA Neurol. 2021;78(3):351-364. doi:10.1001/jamaneurol.2020.4689PubMedGoogle ScholarCrossref
Filippi  M , Preziosa  P , Langdon  D ,  et al.  Identifying progression in multiple sclerosis: new perspectives.   Ann Neurol. 2020;88(3):438-452. doi:10.1002/ana.25808 PubMedGoogle ScholarCrossref
Dickens  AM , Larkin  JR , Griffin  JL ,  et al.  A type 2 biomarker separates relapsing-remitting from secondary progressive multiple sclerosis.   Neurology. 2014;83(17):1492-1499. doi:10.1212/WNL.0000000000000905 PubMedGoogle ScholarCrossref
Ziemssen  T , Akgün  K , Brück  W .  Molecular biomarkers in multiple sclerosis.   J Neuroinflammation. 2019;16(1):272. doi:10.1186/s12974-019-1674-2 PubMedGoogle ScholarCrossref
Ontaneda  D , Fox  RJ , Chataway  J .  Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives.   Lancet Neurol. 2015;14(2):208-223. doi:10.1016/S1474-4422(14)70264-9 PubMedGoogle ScholarCrossref
Cook  NR .  Use and misuse of the receiver operating characteristic curve in risk prediction.   Circulation. 2007;115(7):928-935. doi:10.1161/CIRCULATIONAHA.106.672402 PubMedGoogle ScholarCrossref
Dias  AM , Correia  A , Pereira  MS ,  et al.  Metabolic control of T cell immune response through glycans in inflammatory bowel disease.   Proc Natl Acad Sci U S A. 2018;115(20):E4651-E4660. doi:10.1073/pnas.1720409115 PubMedGoogle ScholarCrossref
Patnaik  SK , Potvin  B , Carlsson  S , Sturm  D , Leffler  H , Stanley  P .  Complex N-glycans are the major ligands for galectin-1, -3, and -8 on Chinese hamster ovary cells.   Glycobiology. 2006;16(4):305-317. doi:10.1093/glycob/cwj063 PubMedGoogle ScholarCrossref
Starossom  SC , Mascanfroni  ID , Imitola  J ,  et al.  Galectin-1 deactivates classically activated microglia and protects from inflammation-induced neurodegeneration.   Immunity. 2012;37(2):249-263. doi:10.1016/j.immuni.2012.05.023 PubMedGoogle ScholarCrossref
Pedersen  HK , Gudmundsdottir  V , Nielsen  HB ,  et al; MetaHIT Consortium.  Human gut microbes impact host serum metabolome and insulin sensitivity.   Nature. 2016;535(7612):376-381. doi:10.1038/nature18646 PubMedGoogle ScholarCrossref
Back  SA , Tuohy  TM , Chen  H ,  et al.  Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation.   Nat Med. 2005;11(9):966-972. doi:10.1038/nm1279 PubMedGoogle ScholarCrossref
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