CoChat
Sign Up
Cited by 70Sphingolipid Metabolism and SignalingMultiple Sclerosis Research StudiesLysosomal Storage Disorders Research

Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation

Open access
Chung, Hyung-lok, Ye, Qi, Park, Ye-Jin, Zuo, Zhongyuan, Mok, Jung-Wan, Kanca, Oguz, Tattikota, Sudhir Gopal, Lu, Shenzhao +3 more·2023·Cell Metabolism
DOI 10.1016/j.cmet.2023.03.022PMC PMC10160010
Open this paper in CoChat — free account

Abstract

VLCFAs (very-long-chain fatty acids) are the most abundant fatty acids in myelin. Hence, during demyelination or aging, glia are exposed to higher levels of VLCFA than normal. We report that glia convert these VLCFA into sphingosine-1-phosphate (S1P) via a glial-specific S1P pathway. Excess S1P causes neuroinflammation, NF-κB activation, and macrophage infiltration into the CNS. Suppressing the function of S1P in fly glia or neurons, or administration of Fingolimod, an S1P receptor antagonist, strongly attenuates the phenotypes caused by excess VLCFAs. In contrast, elevating the VLCFA levels in glia and immune cells exacerbates these phenotypes. Elevated VLCFA and S1P are also toxic in vertebrates based on a mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). Indeed, reducing VLCFA with bezafibrate ameliorates the phenotypes. Moreover, simultaneous use of bezafibrate and fingolimod synergizes to improve EAE, suggesting that lowering VLCFA and S1P is a treatment avenue for MS.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cmet.2023.03.022

Cites

8 of 8 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • VLCFA accumulation in OLs is noxious to the CNS, as OLs can transport S1P to axons.

    “In the fly brain, increased S1P—not VLCFA accumulation per se—triggers direct axonal loss, stimulation of immune cells, and neuroinflammation [273], meaning that VLCFA accumulation in OLs is noxious to the CNS, as they can transport S1P to axons [273].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [273]

    The Results section, “S1P is transported from glia to neuron” (page not provided), reports that S1P produced in fly glia reaches neurons. The Discussion, “VLCFA toxicity in glia” (page not provided), notes that oligodendrocytes express genes in the S1P pathway. The paper does not establish that oligodendrocytes specifically transport S1P to axons, so that part of the citing sentence is an extrapolation. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Elevated S1P is also toxic in vertebrates.

    “Elevated S1P is also toxic in vertebrates [273].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [273]

    The Results section, “S1P induces the demise of neurons” (page unavailable), reports that humans with SGPL1 loss have elevated S1P and neurologic phenotypes. The paper’s experimental evidence that elevated S1P causes toxicity comes from flies, however; the human association does not establish that elevated S1P itself is toxic in vertebrates. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • In Drosophila, increased S1P-not VLCFA accumulation per se-triggers direct axonal loss, stimulation of immune cells, and neuroinflammation.

    “In the fly brain, increased S1P—not VLCFA accumulation per se—triggers direct axonal loss, stimulation of immune cells, and neuroinflammation [273], meaning that VLCFA accumulation in OLs is noxious to the CNS, as they can transport S1P to axons [273].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [273]

    The Introduction and the Discussion’s “Immune activation and neuroinflammation” section report that elevated glial S1P is toxic to neurons and drives immune activation, macrophage recruitment, and neuroinflammation in flies, rather than VLCFA accumulation alone. The copy does not establish direct axonal loss in flies: its reference to axonal damage concerns inflammatory responses during MS. It shows S1P transfer from fly glia to neurons, not specifically from oligodendrocytes to axons. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 132

  1. [1]Nave KA (2010). Myelination and support of axonal integrity by glia. Nature 468, 244– 252. 10.1038/nature09614. 21068833 · DOI · Paper page
  2. [2]Chrast R, Saher G, Nave KA, and Verheijen MH (2011). Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models. J Lipid Res 52, 419– 434. 10.1194/jlr.R009761. 21062955 PMC3035679 · DOI · Paper page
  3. [3]Williams KA, and Deber CM (1993). The structure and function of central nervous system myelin. Crit Rev Clin Lab Sci 30, 29– 64. 10.3109/10408369309084665. 7683887 · DOI · Paper page
  4. [4]O’Brien JS (1965). Stability of the Myelin Membrane. Science 147, 1099– 1107. 10.1126/science.147.3662.1099. 14242030 · DOI
  5. [5]Norton WT, and Poduslo SE (1973). Myelination in rat brain: changes in myelin composition during brain maturation. J Neurochem 21, 759– 773. 10.1111/j.1471-4159.1973.tb07520.x. 4754856 · DOI
  6. [6]Garbay B, Heape AM, Sargueil F, and Cassagne C (2000). Myelin synthesis in the peripheral nervous system. Prog Neurobiol 61, 267– 304. 10.1016/s0301-0082(99)00049-0. 10727776 · DOI
  7. [7]Aggarwal S, Yurlova L, and Simons M (2011). Central nervous system myelin: structure, synthesis and assembly. Trends Cell Biol 21, 585– 593. 10.1016/j.tcb.2011.06.004. 21763137 · DOI · Paper page
  8. [8]Weinstock NI, Shin D, Dhimal N, Hong X, Irons EE, Silvestri NJ, Reed CB, Nguyen D, Sampson O, Cheng YC, (2020). Macrophages Expressing GALC Improve Peripheral Krabbe Disease by a Mechanism Independent of Cross-Correction. Neuron 107, 65– 81 e69. 10.1016/j.neuron.2020.03.031. 32375064 PMC7924901 · DOI
  9. [9]Weinstock NI, Kreher C, Favret J, Nguyen D, Bongarzone ER, Wrabetz L, Feltri ML, and Shin D (2020). Brainstem development requires galactosylceramidase and is critical for pathogenesis in a model of Krabbe disease. Nat Commun 11, 5356. 10.1038/s41467-020-19179-w. 33097716 PMC7584660 · DOI
  10. [10]Sassa T, Suto S, Okayasu Y, and Kihara A (2012). A shift in sphingolipid composition from C24 to C16 increases susceptibility to apoptosis in HeLa cells. Biochim Biophys Acta 1821, 1031– 1037. 10.1016/j.bbalip.2012.04.008. 22579584 · DOI · Paper page
  11. [12]Imgrund S, Hartmann D, Farwanah H, Eckhardt M, Sandhoff R, Degen J, Gieselmann V, Sandhoff K, and Willecke K (2009). Adult ceramide synthase 2 (CERS2)-deficient mice exhibit myelin sheath defects, cerebellar degeneration, and hepatocarcinomas. J Biol Chem 284, 33549– 33560. 10.1074/jbc.M109.031971. 19801672 PMC2785198 · DOI · Paper page
  12. [13]Simons K, and Ikonen E (1997). Functional rafts in cell membranes. Nature 387, 569– 572. 10.1038/42408. 9177342 · DOI · Paper page
  13. [15]Milhas D, Clarke CJ, and Hannun YA (2010). Sphingomyelin metabolism at the plasma membrane: implications for bioactive sphingolipids. FEBS Lett 584, 1887– 1894. 10.1016/j.febslet.2009.10.058. 19857494 PMC2856805 · DOI
  14. [16]Slotte JP (2013). Biological functions of sphingomyelins. Prog Lipid Res 52, 424– 437. 10.1016/j.plipres.2013.05.001. 23684760 · DOI
  15. [17]Bennett ML, Bennett FC, Liddelow SA, Ajami B, Zamanian JL, Fernhoff NB, Mulinyawe SB, Bohlen CJ, Adil A, Tucker A, (2016). New tools for studying microglia in the mouse and human CNS. Proc Natl Acad Sci U S A 113, E1738– 1746. 10.1073/pnas.1525528113. 26884166 PMC4812770 · DOI · Paper page
  16. [19]Li H, Janssens J, De Waegeneer M, Kolluru SS, Davie K, Gardeux V, Saelens W, David FPA, Brbic M, Spanier K, (2022). Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly. Science 375, eabk2432. 10.1126/science.abk2432. 35239393 PMC8944923 · DOI
  17. [20]Lin G, Lee PT, Chen K, Mao D, Tan KL, Zuo Z, Lin WW, Wang L, and Bellen HJ (2018). Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to alpha-Synuclein Gain. Cell Metab 28, 605– 618 e606. 10.1016/j.cmet.2018.05.019. 29909971 · DOI
  18. [21]Wang L, Lin G, Zuo Z, Li Y, Byeon SK, Pandey A, and Bellen HJ (2022). Neuronal activity induces glucosylceramide that is secreted via exosomes for lysosomal degradation in glia. Sci Adv 8, eabn3326. 10.1126/sciadv.abn3326. 35857503 PMC9278864 · DOI
  19. [22]Yuan C, Rao RP, Jesmin N, Bamba T, Nagashima K, Pascual A, Preat T, Fukusaki E, Acharya U, and Acharya JK (2011). CDase is a pan-ceramidase in Drosophila. Mol Biol Cell 22, 33– 43. 10.1091/mbc.E10-05-0453. 21148295 PMC3016975 · DOI
  20. [23]Acharya JK, Dasgupta U, Rawat SS, Yuan C, Sanxaridis PD, Yonamine I, Karim P, Nagashima K, Brodsky MH, Tsunoda S, and Acharya U (2008). Cell-nonautonomous function of ceramidase in photoreceptor homeostasis. Neuron 57, 69– 79. 10.1016/j.neuron.2007.10.041. 18184565 PMC2271043 · DOI
  21. [24]Ghosh A, Kling T, Snaidero N, Sampaio JL, Shevchenko A, Gras H, Geurten B, Gopfert MC, Schulz JB, Voigt A, and Simons M (2013). A global in vivo Drosophila RNAi screen identifies a key role of ceramide phosphoethanolamine for glial ensheathment of axons. PLoS Genet 9, e1003980. 10.1371/journal.pgen.1003980. 24348263 PMC3861124 · DOI
  22. [25]Peters R (2006). Ageing and the brain. Postgrad Med J 82, 84– 88. 10.1136/pgmj.2005.036665. 16461469 PMC2596698 · DOI · Paper page
  23. [26]Nasrabady SE, Rizvi B, Goldman JE, and Brickman AM (2018). White matter changes in Alzheimer’s disease: a focus on myelin and oligodendrocytes. Acta Neuropathol Commun 6, 22. 10.1186/s40478-018-0515-3. 29499767 PMC5834839 · DOI · Paper page
  24. [27]Bae HG, Kim TK, Suk HY, Jung S, and Jo DG (2020). White matter and neurological disorders. Arch Pharm Res 43, 920– 931. 10.1007/s12272-020-01270-x. 32975736 · DOI
  25. [28]Chung HL, Wangler MF, Marcogliese PC, Jo J, Ravenscroft TA, Zuo Z, Duraine L, Sadeghzadeh S, Li-Kroeger D, Schmidt RE, (2020). Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms. Neuron. 10.1016/j.neuron.2020.02.021. PMC7289150 32169171 · DOI · Paper page
  26. [29]Watkins PA, McGuinness MC, Raymond GV, Hicks BA, Sisk JM, Moser AB, and Moser HW (1995). Distinction between peroxisomal bifunctional enzyme and acyl-CoA oxidase deficiencies. Ann Neurol 38, 472– 477. 10.1002/ana.410380322. 7668838 · DOI
  27. [30]Engelen M, Schackmann MJ, Ofman R, Sanders RJ, Dijkstra IM, Houten SM, Fourcade S, Pujol A, Poll-The BT, Wanders RJ, and Kemp S (2012). Bezafibrate lowers very long-chain fatty acids in X-linked adrenoleukodystrophy fibroblasts by inhibiting fatty acid elongation. J Inherit Metab Dis 35, 1137– 1145. 10.1007/s10545-012-9471-4. 22447153 PMC3470694 · DOI
  28. [31]Engelen M, Tran L, Ofman R, Brennecke J, Moser AB, Dijkstra IM, Wanders RJ, Poll-The BT, and Kemp S (2012). Bezafibrate for X-linked adrenoleukodystrophy. PLoS One 7, e41013. 10.1371/journal.pone.0041013. 22911730 PMC3401223 · DOI
  29. [33]Kremer MC, Jung C, Batelli S, Rubin GM, and Gaul U (2017). The glia of the adult Drosophila nervous system. Glia 65, 606– 638. 10.1002/glia.23115. 28133822 PMC5324652 · DOI
  30. [34]Siow DL, and Wattenberg BW (2012). Mammalian ORMDL proteins mediate the feedback response in ceramide biosynthesis. J Biol Chem 287, 40198– 40204. 10.1074/jbc.C112.404012. 23066021 PMC3504734 · DOI
  31. [35]Davis DL, Gable K, Suemitsu J, Dunn TM, and Wattenberg BW (2019). The ORM-DL/Orm-serine palmitoyltransferase (SPT) complex is directly regulated by ceramide: Reconstitution of SPT regulation in isolated membranes. J Biol Chem 294, 5146– 5156. 10.1074/jbc.RA118.007291. 30700557 PMC6442065 · DOI
  32. [36]Acharya U, and Acharya JK (2005). Enzymes of sphingolipid metabolism in Drosophila melanogaster. Cell Mol Life Sci 62, 128– 142. 10.1007/s00018-004-4254-1. 15666085 PMC11924467 · DOI
  33. [37]Bauer R, Voelzmann A, Breiden B, Schepers U, Farwanah H, Hahn I, Eckardt F, Sandhoff K, and Hoch M (2009). Schlank, a member of the ceramide synthase family controls growth and body fat in Drosophila. EMBO J 28, 3706– 3716. 10.1038/emboj.2009.305. 19834458 PMC2790492 · DOI
  34. [38]Mao C, and Obeid LM (2008). Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate. Biochim Biophys Acta 1781, 424– 434. 10.1016/j.bbalip.2008.06.002. 18619555 PMC2614331 · DOI
  35. [39]Rosen H, and Goetzl EJ (2005). Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network. Nat Rev Immunol 5, 560– 570. 10.1038/nri1650. 15999095 · DOI
  36. [40]Aguilar A, and Saba JD (2012). Truth and consequences of sphingosine-1-phosphate lyase. Adv Biol Regul 52, 17– 30. 10.1016/j.advenzreg.2011.09.015. 21946005 PMC3560305 · DOI
  37. [41]Wang J, Al-Ouran R, Hu Y, Kim SY, Wan YW, Wangler MF, Yamamoto S, Chao HT, Comjean A, Mohr SE, (2017). MARRVEL: Integration of Human and Model Organism Genetic Resources to Facilitate Functional Annotation of the Human Genome. Am J Hum Genet 100, 843– 853. 10.1016/j.ajhg.2017.04.010. 28502612 PMC5670038 · DOI
  38. [42]Liu T, Sims D, and Baum B (2009). Parallel RNAi screens across different cell lines identify generic and cell type-specific regulators of actin organization and cell morphology. Genome Biol 10, R26. 10.1186/gb-2009-10-3-r26. 19265526 PMC2690997 · DOI
  39. [43]Schnorrer F, Schonbauer C, Langer CC, Dietzl G, Novatchkova M, Schernhuber K, Fellner M, Azaryan A, Radolf M, Stark A, (2010). Systematic genetic analysis of muscle morphogenesis and function in Drosophila. Nature 464, 287– 291. 10.1038/nature08799. 20220848 · DOI
  40. [44]Wicker-Thomas C, Garrido D, Bontonou G, Napal L, Mazuras N, Denis B, Rubin T, Parvy JP, and Montagne J (2015). Flexible origin of hydrocarbon/pheromone precursors in Drosophila melanogaster. J Lipid Res 56, 2094– 2101. 10.1194/jlr.M060368. 26353752 PMC4617396 · DOI
  41. [45]Kanca O, Zirin J, Garcia-Marques J, Knight SM, Yang-Zhou D, Amador G, Chung H, Zuo Z, Ma L, He Y, (2019). An efficient CRISPR-based strategy to insert small and large fragments of DNA using short homology arms. Elife 8. 10.7554/eLife.51539. PMC6855806 31674908 · DOI
  42. [46]Kanca O, Zirin J, Hu Y, Tepe B, Dutta D, Lin WW, Ma L, Ge M, Zuo Z, Liu LP, (2022). An expanded toolkit for Drosophila gene tagging using synthesized homology donor constructs for CRISPR-mediated homologous recombination. Elife 11. 10.7554/eLife.76077. PMC9239680 35723254 · DOI
  43. [47]Davie K, Janssens J, Koldere D, De Waegeneer M, Pech U, Kreft L, Aibar S, Makhzami S, Christiaens V, Bravo Gonzalez-Blas C, (2018). A Single-Cell Transcriptome Atlas of the Aging Drosophila Brain. Cell 174, 982– 998 e920. 10.1016/j.cell.2018.05.057. 29909982 PMC6086935 · DOI · Paper page
  44. [49]Spiegel S, and Milstien S (2003). Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol 4, 397– 407. 10.1038/nrm1103. 12728273 · DOI
  45. [50]Taha TA, Argraves KM, and Obeid LM (2004). Sphingosine-1-phosphate receptors: receptor specificity versus functional redundancy. Biochim Biophys Acta 1682, 48– 55. 10.1016/j.bbalip.2004.01.006. 15158755 · DOI
  46. [51]Maceyka M, Harikumar KB, Milstien S, and Spiegel S (2012). Sphingosine-1-phosphate signaling and its role in disease. Trends Cell Biol 22, 50– 60. 10.1016/j.tcb.2011.09.003. 22001186 PMC3253987 · DOI · Paper page
  47. [52]Goto H, Miyamoto M, and Kihara A (2021). Direct uptake of sphingosine-1-phosphate independent of phospholipid phosphatases. J Biol Chem 296, 100605. 10.1016/j.jbc.2021.100605. 33785361 PMC8093947 · DOI
  48. [53]Di Pardo A, Pepe G, Castaldo S, Marracino F, Capocci L, Amico E, Madonna M, Giova S, Jeong SK, Park BM, (2019). Stimulation of Sphingosine Kinase 1 (SPHK1) Is Beneficial in a Huntington’s Disease Pre-clinical Model. Front Mol Neurosci 12, 100. 10.3389/fnmol.2019.00100. 31068790 PMC6491579 · DOI
  49. [54]Di Pardo A, and Maglione V (2018). Sphingolipid Metabolism: A New Therapeutic Opportunity for Brain Degenerative Disorders. Front Neurosci 12, 249. 10.3389/fnins.2018.00249. 29719499 PMC5913346 · DOI
  50. [55]Grassi S, Mauri L, Prioni S, Cabitta L, Sonnino S, Prinetti A, and Giussani P (2019). Sphingosine 1-Phosphate Receptors and Metabolic Enzymes as Druggable Targets for Brain Diseases. Front Pharmacol 10, 807. 10.3389/fphar.2019.00807. 31427962 PMC6689979 · DOI
  51. [56]Karaca I, Tamboli IY, Glebov K, Richter J, Fell LH, Grimm MO, Haupenthal VJ, Hartmann T, Graler MH, van Echten-Deckert G, and Walter J (2014). Deficiency of sphingosine-1-phosphate lyase impairs lysosomal metabolism of the amyloid precursor protein. J Biol Chem 289, 16761– 16772. 10.1074/jbc.M113.535500. 24808180 PMC4059120 · DOI
  52. [57]Proia RL, and Hla T (2015). Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest 125, 1379– 1387. 10.1172/JCI76369. 25831442 PMC4409021 · DOI
  53. [58]Pantoja M, Fischer KA, Ieronimakis N, Reyes M, and Ruohola-Baker H (2013). Genetic elevation of sphingosine 1-phosphate suppresses dystrophic muscle phenotypes in Drosophila. Development 140, 136– 146. 10.1242/dev.087791. 23154413 PMC3513996 · DOI
  54. [59]Lovric S, Goncalves S, Gee HY, Oskouian B, Srinivas H, Choi WI, Shril S, Ashraf S, Tan W, Rao J, (2017). Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency. J Clin Invest 127, 912– 928. 10.1172/JCI89626. 28165339 PMC5330730 · DOI
  55. [60]Janecke AR, Xu R, Steichen-Gersdorf E, Waldegger S, Entenmann A, Giner T, Krainer I, Huber LA, Hess MW, Frishberg Y, (2017). Deficiency of the sphingosine-1-phosphate lyase SGPL1 is associated with congenital nephrotic syndrome and congenital adrenal calcifications. Hum Mutat 38, 365– 372. 10.1002/humu.23192. 28181337 PMC5384969 · DOI
  56. [61]Prasad R, Hadjidemetriou I, Maharaj A, Meimaridou E, Buonocore F, Saleem M, Hurcombe J, Bierzynska A, Barbagelata E, Bergada I, (2017). Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome. J Clin Invest 127, 942– 953. 10.1172/JCI90171. 28165343 PMC5330744 · DOI
  57. [62]Hu Y, Flockhart I, Vinayagam A, Bergwitz C, Berger B, Perrimon N, and Mohr SE (2011). An integrative approach to ortholog prediction for disease-focused and other functional studies. BMC Bioinformatics 12, 357. 10.1186/1471-2105-12-357. 21880147 PMC3179972 · DOI
  58. [63]Lai SL, and Lee T (2006). Genetic mosaic with dual binary transcriptional systems in Drosophila. Nat Neurosci 9, 703– 709. 10.1038/nn1681. 16582903 · DOI
  59. [64]Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G, Aradhye S, and Burtin P (2010). Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov 9, 883– 897. 10.1038/nrd3248. 21031003 · DOI · Paper page
  60. [65]Yamamoto S, Jaiswal M, Charng WL, Gambin T, Karaca E, Mirzaa G, Wiszniewski W, Sandoval H, Haelterman NA, Xiong B, (2014). A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases. Cell 159, 200– 214. 10.1016/j.cell.2014.09.002. 25259927 PMC4298142 · DOI
  61. [66]Liu L, MacKenzie KR, Putluri N, Maletic-Savatic M, and Bellen HJ (2017). The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D. Cell Metab 26, 719– 737 e716. 10.1016/j.cmet.2017.08.024. 28965825 PMC5677551 · DOI · Paper page
  62. [67]Moulton MJ, Barish S, Ralhan I, Chang J, Goodman LD, Harland JG, Marcogliese PC, Johansson JO, Ioannou MS, and Bellen HJ (2021). Neuronal ROS-induced glial lipid droplet formation is altered by loss of Alzheimer’s disease-associated genes. Proc Natl Acad Sci U S A 118. 10.1073/pnas.2112095118. PMC8719885 34949639 · DOI · Paper page
  63. [68]Hardie RC, and Raghu P (2001). Visual transduction in Drosophila. Nature 413, 186– 193. 10.1038/35093002. 11557987 · DOI
  64. [69]Vacaru AM, van den Dikkenberg J, Ternes P, and Holthuis JC (2013). Ceramide phosphoethanolamine biosynthesis in Drosophila is mediated by a unique ethanolamine phosphotransferase in the Golgi lumen. J Biol Chem 288, 11520– 11530. 10.1074/jbc.M113.460972. 23449981 PMC3630839 · DOI
  65. [70]Freeman MR (2015). Drosophila Central Nervous System Glia. Cold Spring Harb Perspect Biol 7. 10.1101/cshperspect.a020552. PMC4632667 25722465 · DOI · Paper page
  66. [71]MacDonald JM, Beach MG, Porpiglia E, Sheehan AE, Watts RJ, and Freeman MR (2006). The Drosophila cell corpse engulfment receptor Draper mediates glial clearance of severed axons. Neuron 50, 869– 881. 10.1016/j.neuron.2006.04.028. 16772169 · DOI · Paper page
  67. [72]Hakim-Mishnaevski K, Flint-Brodsly N, Shklyar B, Levy-Adam F, and Kurant E (2019). Glial Phagocytic Receptors Promote Neuronal Loss in Adult Drosophila Brain. Cell Rep 29, 1438– 1448 e1433. 10.1016/j.celrep.2019.09.086. 31693886 · DOI
  68. [73]Doherty J, Logan MA, Tasdemir OE, and Freeman MR (2009). Ensheathing glia function as phagocytes in the adult Drosophila brain. J Neurosci 29, 4768– 4781. 10.1523/JNEUROSCI.5951-08.2009. 19369546 PMC2674269 · DOI
  69. [74]Ziegenfuss JS, Biswas R, Avery MA, Hong K, Sheehan AE, Yeung YG, Stanley ER, and Freeman MR (2008). Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling. Nature 453, 935– 939. 10.1038/nature06901. 18432193 PMC2493287 · DOI
  70. [75]Choi JW, Gardell SE, Herr DR, Rivera R, Lee CW, Noguchi K, Teo ST, Yung YC, Lu M, Kennedy G, and Chun J (2011). FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation. Proc Natl Acad Sci U S A 108, 751– 756. 10.1073/pnas.1014154108. 21177428 PMC3021041 · DOI
  71. [76]Stofanko M, Kwon SY, and Badenhorst P (2010). Lineage tracing of lamellocytes demonstrates Drosophila macrophage plasticity. PLoS One 5, e14051. 10.1371/journal.pone.0014051. 21124962 PMC2988793 · DOI
  72. [77]Galko MJ, and Krasnow MA (2004). Cellular and genetic analysis of wound healing in Drosophila larvae. PLoS Biol 2, E239. 10.1371/journal.pbio.0020239. 15269788 PMC479041 · DOI
  73. [78]De Gregorio E, Han SJ, Lee WJ, Baek MJ, Osaki T, Kawabata S, Lee BL, Iwanaga S, Lemaitre B, and Brey PT (2002). An immune-responsive Serpin regulates the melanization cascade in Drosophila. Dev Cell 3, 581– 592. 10.1016/s1534-5807(02)00267-8. 12408809 · DOI
  74. [79]Tang H (2009). Regulation and function of the melanization reaction in Drosophila. Fly (Austin) 3, 105– 111. 10.4161/fly.3.1.7747. 19164947 · DOI
  75. [80]Shaukat Z, Liu D, and Gregory S (2015). Sterile inflammation in Drosophila. Mediators Inflamm 2015, 369286. 10.1155/2015/369286. 25948885 PMC4408615 · DOI
  76. [81]Hoffmann JA (2003). The immune response of Drosophila. Nature 426, 33– 38. 10.1038/nature02021. 14603309 · DOI · Paper page
  77. [82]Roth S, Hiromi Y, Godt D, and Nusslein-Volhard C (1991). cactus, a maternal gene required for proper formation of the dorsoventral morphogen gradient in Drosophila embryos. Development 112, 371– 388. 10.1242/dev.112.2.371. 1794309 · DOI
  78. [83]Kaneko T, Yano T, Aggarwal K, Lim JH, Ueda K, Oshima Y, Peach C, Erturk-Hasdemir D, Goldman WE, Oh BH, (2006). PGRP-LC and PGRP-LE have essential yet distinct functions in the drosophila immune response to monomeric DAP-type peptidoglycan. Nat Immunol 7, 715– 723. 10.1038/ni1356. 16767093 · DOI
  79. [84]Gottar M, Gobert V, Michel T, Belvin M, Duyk G, Hoffmann JA, Ferrandon D, and Royet J (2002). The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature 416, 640– 644. 10.1038/nature734. 11912488 · DOI
  80. [85]Busse MS, Arnold CP, Towb P, Katrivesis J, and Wasserman SA (2007). A kappaB sequence code for pathway-specific innate immune responses. EMBO J 26, 3826– 3835. 10.1038/sj.emboj.7601798. 17660749 PMC1952218 · DOI
  81. [86]Winkler B, Funke D, Benmimoun B, Speder P, Rey S, Logan MA, and Klambt C (2021). Brain inflammation triggers macrophage invasion across the blood-brain barrier in Drosophila during pupal stages. Sci Adv 7, eabh0050. 10.1126/sciadv.abh0050. 34705495 PMC8550232 · DOI · Paper page
  82. [87]Koyle ML, Veloz M, Judd AM, Wong AC, Newell PD, Douglas AE, and Chaston JM (2016). Rearing the Fruit Fly Drosophila melanogaster Under Axenic and Gnotobiotic Conditions. J Vis Exp. 10.3791/54219. PMC5091700 27500374 · DOI
  83. [88]Sinenko SA, and Mathey-Prevot B (2004). Increased expression of Drosophila tetraspanin, Tsp68C, suppresses the abnormal proliferation of ytr-deficient and Ras/Raf-activated hemocytes. Oncogene 23, 9120– 9128. 10.1038/sj.onc.1208156. 15480416 · DOI
  84. [89]Boulet M, Renaud Y, Lapraz F, Benmimoun B, Vandel L, and Waltzer L (2021). Characterization of the Drosophila Adult Hematopoietic System Reveals a Rare Cell Population With Differentiation and Proliferation Potential. Front Cell Dev Biol 9, 739357. 10.3389/fcell.2021.739357. 34722521 PMC8550105 · DOI
  85. [90]Prinz M, and Priller J (2017). The role of peripheral immune cells in the CNS in steady state and disease. Nat Neurosci 20, 136– 144. 10.1038/nn.4475. 28092660 · DOI · Paper page
  86. [91]Poll-The BT, Roels F, Ogier H, Scotto J, Vamecq J, Schutgens RB, Wanders RJ, van Roermund CW, van Wijland MJ, Schram AW, and (1988). A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodystrophy). Am J Hum Genet 42, 422– 434. 2894756 PMC1715143
  87. [92]Constantinescu CS, Farooqi N, O’Brien K, and Gran B (2011). Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol 164, 1079– 1106. 10.1111/j.1476-5381.2011.01302.x. 21371012 PMC3229753 · DOI · Paper page
  88. [93]Baecher-Allan C, Kaskow BJ, and Weiner HL (2018). Multiple Sclerosis: Mechanisms and Immunotherapy. Neuron 97, 742– 768. 10.1016/j.neuron.2018.01.021. 29470968 · DOI · Paper page
  89. [94]Roggeri A, Schepers M, Tiane A, Rombaut B, van Veggel L, Hellings N, Prickaerts J, Pittaluga A, and Vanmierlo T (2020). Sphingosine-1-Phosphate Receptor Modulators and Oligodendroglial Cells: Beyond Immunomodulation. Int J Mol Sci 21. 10.3390/ijms21207537. PMC7588977 33066042 · DOI
  90. [95]Dukala DE, and Soliven B (2016). S1P1 deletion in oligodendroglial lineage cells: Effect on differentiation and myelination. Glia 64, 570– 582. 10.1002/glia.22949. 26662919 · DOI
  91. [96]Subei AM, and Cohen JA (2015). Sphingosine 1-phosphate receptor modulators in multiple sclerosis. CNS Drugs 29, 565– 575. 10.1007/s40263-015-0261-z. 26239599 PMC4554772 · DOI
  92. [97]Volpi C, Orabona C, Macchiarulo A, Bianchi R, Puccetti P, and Grohmann U (2019). Preclinical discovery and development of fingolimod for the treatment of multiple sclerosis. Expert Opin Drug Discov 14, 1199– 1212. 10.1080/17460441.2019.1646244. 31389262 · DOI
  93. [98]Zhang Y, Li X, Ciric B, Ma CG, Gran B, Rostami A, and Zhang GX (2017). Effect of Fingolimod on Neural Stem Cells: A Novel Mechanism and Broadened Application for Neural Repair. Mol Ther 25, 401– 415. 10.1016/j.ymthe.2016.12.008. 28153091 PMC5368668 · DOI
  94. [99]Vogelaar CF, Mandal S, Lerch S, Birkner K, Birkenstock J, Buhler U, Schnatz A, Raine CS, Bittner S, Vogt J, (2018). Fast direct neuronal signaling via the IL-4 receptor as therapeutic target in neuroinflammation. Sci Transl Med 10. 10.1126/scitranslmed.aao2304. PMC12102061 29491183 · DOI
  95. [100]Wang H, Newton G, Wu L, Lin LL, Miracco AS, Natesan S, and Luscinskas FW (2021). CD47 antibody blockade suppresses microglia-dependent phagocytosis and monocyte transition to macrophages, impairing recovery in EAE. JCI Insight 6. 10.1172/jci.insight.148719. PMC8663579 34591795 · DOI
  96. [101]Wagner CA, Roque PJ, Mileur TR, Liggitt D, and Goverman JM (2020). Myelin-specific CD8+ T cells exacerbate brain inflammation in CNS autoimmunity. J Clin Invest 130, 203– 213. 10.1172/JCI132531. 31573979 PMC6934187 · DOI
  97. [102]Babbe H, Roers A, Waisman A, Lassmann H, Goebels N, Hohlfeld R, Friese M, Schroder R, Deckert M, Schmidt S, (2000). Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. J Exp Med 192, 393– 404. 10.1084/jem.192.3.393. 10934227 PMC2193223 · DOI · Paper page
  98. [103]Jacobsen M, Cepok S, Quak E, Happel M, Gaber R, Ziegler A, Schock S, Oertel WH, Sommer N, and Hemmer B (2002). Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients. Brain 125, 538– 550. 10.1093/brain/awf059. 11872611 · DOI
  99. [104]MacBrinn MC, and O’Brien JS (1969). Lipid composition of optic nerve myelin. J Neurochem 16, 7– 12. 10.1111/j.1471-4159.1969.tb10337.x. 5776614 · DOI
  100. [105]Manor J, Chung H, Bhagwat PK, and Wangler MF (2021). ABCD1 and X-linked adrenoleukodystrophy: A disease with a markedly variable phenotype showing conserved neurobiology in animal models. J Neurosci Res 99, 3170– 3181. 10.1002/jnr.24953. 34716609 PMC9665428 · DOI
  101. [106]Guttenplan KA, Weigel MK, Prakash P, Wijewardhane PR, Hasel P, Rufen-Blanchette U, Munch AE, Blum JA, Fine J, Neal MC, (2021). Neurotoxic reactive astrocytes induce cell death via saturated lipids. Nature 599, 102– 107. 10.1038/s41586-021-03960-y. 34616039 PMC12054010 · DOI · Paper page
  102. [107]Robinson RR, Dietz AK, Maroof AM, Asmis R, and Forsthuber TG (2019). The role of glial-neuronal metabolic cooperation in modulating progression of multiple sclerosis and neuropathic pain. Immunotherapy 11, 129– 147. 10.2217/imt-2018-0153. 30730270 PMC6354220 · DOI
  103. [108]Fukuhara S, Simmons S, Kawamura S, Inoue A, Orba Y, Tokudome T, Sunden Y, Arai Y, Moriwaki K, Ishida J, (2012). The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice. J Clin Invest 122, 1416– 1426. 10.1172/JCI60746. 22406534 PMC3314466 · DOI
  104. [109]Dermaut B, Norga KK, Kania A, Verstreken P, Pan H, Zhou Y, Callaerts P, and Bellen HJ (2005). Aberrant lysosomal carbohydrate storage accompanies endocytic defects and neurodegeneration in Drosophila benchwarmer. J Cell Biol 170, 127– 139. 10.1083/jcb.200412001. 15998804 PMC2171373 · DOI
  105. [110]Yuva-Aydemir Y, Bauke AC, and Klambt C (2011). Spinster controls Dpp signaling during glial migration in the Drosophila eye. J Neurosci 31, 7005– 7015. 10.1523/JNEUROSCI.0459-11.2011. 21562262 PMC6703225 · DOI
  106. [111]Blaho VA, and Hla T (2014). An update on the biology of sphingosine 1-phosphate receptors. J Lipid Res 55, 1596– 1608. 10.1194/jlr.R046300. 24459205 PMC4109755 · DOI · Paper page
  107. [112]Bruck W, Sommermeier N, Bergmann M, Zettl U, Goebel HH, Kretzschmar HA, and Lassmann H (1996). Macrophages in multiple sclerosis. Immunobiology 195, 588– 600. 10.1016/S0171-2985(96)80024-6. 8933159 · DOI · Paper page
  108. [113]Chitnis T, and Weiner HL (2017). CNS inflammation and neurodegeneration. J Clin Invest 127, 3577– 3587. 10.1172/JCI90609. 28872464 PMC5617655 · DOI
  109. [114]Kulakowska A, Zendzian-Piotrowska M, Baranowski M, Kononczuk T, Drozdowski W, Gorski J, and Bucki R (2010). Intrathecal increase of sphingosine 1-phosphate at early stage multiple sclerosis. Neurosci Lett 477, 149– 152. 10.1016/j.neulet.2010.04.052. 20434523 · DOI
  110. [115]Deplanque D, Gele P, Petrault O, Six I, Furman C, Bouly M, Nion S, Dupuis B, Leys D, Fruchart JC, (2003). Peroxisome proliferator-activated receptor-alpha activation as a mechanism of preventive neuroprotection induced by chronic fenofibrate treatment. J Neurosci 23, 6264– 6271. 10.1523/JNEUROSCI.23-15-06264.2003. 12867511 PMC6740545 · DOI
  111. [116]Foster CA, Howard LM, Schweitzer A, Persohn E, Hiestand PC, Balatoni B, Reuschel R, Beerli C, Schwartz M, and Billich A (2007). Brain penetration of the oral immunomodulatory drug FTY720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: consequences for mode of action in multiple sclerosis. J Pharmacol Exp Ther 323, 469– 475. 10.1124/jpet.107.127183. 17682127 · DOI
  112. [117]Ibanez C, Simo C, Barupal DK, Fiehn O, Kivipelto M, Cedazo-Minguez A, and Cifuentes A (2013). A new metabolomic workflow for early detection of Alzheimer’s disease. J Chromatogr A 1302, 65– 71. 10.1016/j.chroma.2013.06.005. 23827464 · DOI
  113. [118]Baloni P, Arnold M, Moreno H, Nho K, Buitrago L, Huynh K, Brauner B, Louie G, Kueider-Paisley A, Suhre K, (2021). Multi-Omic Analyses Characterize the Ceramide/Sphingomyelin Pathway as a Therapeutic Target in Alzheimer’s Disease. 2021.2007.2016.21260601. 10.1101/2021.07.16.21260601 % J medRxiv. PMC9547905 36209301 · DOI
  114. [119]Nakano Y, Fujitani K, Kurihara J, Ragan J, Usui-Aoki K, Shimoda L, Lukacsovich T, Suzuki K, Sezaki M, Sano Y, (2001). Mutations in the novel membrane protein spinster interfere with programmed cell death and cause neural degeneration in Drosophila melanogaster. Mol Cell Biol 21, 3775– 3788. 10.1128/MCB.21.11.3775-3788.2001. 11340170 PMC87027 · DOI
  115. [120]Sweeney ST, and Davis GW (2002). Unrestricted synaptic growth in spinster-a late endosomal protein implicated in TGF-beta-mediated synaptic growth regulation. Neuron 36, 403– 416. 10.1016/s0896-6273(02)01014-0. 12408844 · DOI
  116. [121]Kurucz E, Vaczi B, Markus R, Laurinyecz B, Vilmos P, Zsamboki J, Csorba K, Gateff E, Hultmark D, and Ando I (2007). Definition of Drosophila hemocyte subsets by cell-type specific antigens. Acta Biol Hung 58 Suppl, 95– 111. 10.1556/ABiol.58.2007.Suppl.8. 18297797 · DOI
  117. [122]Diao F, Ironfield H, Luan H, Diao F, Shropshire WC, Ewer J, Marr E, Potter CJ, Landgraf M, and White BH (2015). Plug-and-play genetic access to drosophila cell types using exchangeable exon cassettes. Cell Rep 10, 1410– 1421. 10.1016/j.celrep.2015.01.059. 25732830 PMC4373654 · DOI
  118. [123]Yonamine I, Bamba T, Nirala NK, Jesmin N, Kosakowska-Cholody T, Nagashima K, Fukusaki E, Acharya JK, and Acharya U (2011). Sphingosine kinases and their metabolites modulate endolysosomal trafficking in photoreceptors. J Cell Biol 192, 557– 567. 10.1083/jcb.201004098. 21321100 PMC3044112 · DOI
  119. [124]Tokusumi T, Tokusumi Y, Brahier MS, Lam V, Stoller-Conrad JR, Kroeger PT, and Schulz RA (2017). Screening and Analysis of Janelia FlyLight Project Enhancer-Gal4 Strains Identifies Multiple Gene Enhancers Active During Hematopoiesis in Normal and Wasp-Challenged Drosophila Larvae. G3 (Bethesda) 7, 437– 448. 10.1534/g3.116.034439. 27913635 PMC5295592 · DOI
  120. [125]Gyoergy A, Roblek M, Ratheesh A, Valoskova K, Belyaeva V, Wachner S, Matsubayashi Y, Sanchez-Sanchez BJ, Stramer B, and Siekhaus DE (2018). Tools Allowing Independent Visualization and Genetic Manipulation of Drosophila melanogaster Macrophages and Surrounding Tissues. G3 (Bethesda) 8, 845– 857. 10.1534/g3.117.300452. 29321168 PMC5844306 · DOI
  121. [126]Oswald MC, West RJ, Lloyd-Evans E, and Sweeney ST (2015). Identification of dietary alanine toxicity and trafficking dysfunction in a Drosophila model of hereditary sensory and autonomic neuropathy type 1. Hum Mol Genet 24, 6899– 6909. 10.1093/hmg/ddv390. 26395456 PMC4654049 · DOI
  122. [128]Kondo S, and Ueda R (2013). Highly improved gene targeting by germline-specific Cas9 expression in Drosophila. Genetics 195, 715– 721. 10.1534/genetics.113.156737. 24002648 PMC3813859 · DOI
  123. [129]Park YJ, Kim S, Shim HP, Park JH, Lee G, Kim TY, Jo MC, Kwon AY, Lee M, Lee S, (2021). Phosphatidylserine synthase plays an essential role in glia and affects development, as well as the maintenance of neuronal function. iScience 24, 102899. 10.1016/j.isci.2021.102899. 34401677 PMC8358705 · DOI
  124. [130]Hu Y, Sopko R, Foos M, Kelley C, Flockhart I, Ammeux N, Wang X, Perkins L, Perrimon N, and Mohr SE (2013). FlyPrimerBank: an online database for Drosophila melanogaster gene expression analysis and knockdown evaluation of RNAi reagents. G3 (Bethesda) 3, 1607– 1616. 10.1534/g3.113.007021. 23893746 PMC3755921 · DOI
  125. [131]Chung HL, Augustine GJ, and Choi KW (2016). Drosophila Schip1 Links Expanded and Tao-1 to Regulate Hippo Signaling. Dev Cell 36, 511– 524. 10.1016/j.devcel.2016.02.004. 26954546 · DOI
  126. [132]O’Neill EM, Rebay I, Tjian R, and Rubin GM (1994). The activities of two Ets-related transcription factors required for Drosophila eye development are modulated by the Ras/MAPK pathway. Cell 78, 137– 147. 8033205
  127. [133]Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, (2012). Fiji: an open-source platform for biological-image analysis. Nat Methods 9, 676– 682. 10.1038/nmeth.2019. 22743772 PMC3855844 · DOI · Paper page
  128. [134]Tattikota SG, Cho B, Liu Y, Hu Y, Barrera V, Steinbaugh MJ, Yoon SH, Comjean A, Li F, Dervis F, (2020). A single-cell survey of Drosophila blood. Elife 9. 10.7554/eLife.54818. PMC7237219 32396065 · DOI
  129. [137]McCarthy DP, Richards MH, and Miller SD (2012). Mouse models of multiple sclerosis: experimental autoimmune encephalomyelitis and Theiler’s virus-induced demyelinating disease. Methods Mol Biol 900, 381– 401. 10.1007/978-1-60761-720-4_19. 22933080 PMC3583382 · DOI
  130. [138]Stromnes IM, and Goverman JM (2006). Active induction of experimental allergic encephalomyelitis. Nat Protoc 1, 1810– 1819. 10.1038/nprot.2006.285. 17487163 · DOI
  131. [139]Jo J, Woo J, Cristobal CD, Choi JM, Wang CY, Ye Q, Smith JA, Ung K, Liu G, Cortes D, (2021). Regional heterogeneity of astrocyte morphogenesis dictated by the formin protein, Daam2, modifies circuit function. EMBO Rep 22, e53200. 10.15252/embr.202153200. 34633730 PMC8647146 · DOI
  132. [140]Ding X, Jo J, Wang CY, Cristobal CD, Zuo Z, Ye Q, Wirianto M, Lindeke-Myers A, Choi JM, Mohila CA, (2020). The Daam2-VHL-Nedd4 axis governs developmental and regenerative oligodendrocyte differentiation. Genes Dev 34, 1177– 1189. 10.1101/gad.338046.120. 32792353 PMC7462057 · DOI

Cited by

Sorted by citations

Authors
Chung, H.-L., Ye, Q., Park, Y.-J., Zuo, Z., Mok, J.-W., Kanca, O., Tattikota, S. G., Lu, S., Perrimon, N., Lee, H. K., & Bellen, H. J.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Baylor College of Medicine (US)
  • Harvard University (US)
Corresponding author
  • Chung, Hyung-lok
  • Lee, Hyun Kyoung
  • Bellen, Hugo J.
ORCID
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2023-05
Volume
35
Issue
5
Pages
855-874.e5
ISSN
1550-4131 (ISSN-L)
DOI
10.1016/j.cmet.2023.03.022
PMC
PMC10160010
OpenAlex
W4366520867
Cited by
70
References
8
Citations by year
2026: 17 · 2025: 23 · 2024: 20 · 2023: 10
FWCI
6.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Metabolism (publishedVersion)
  • SSRN Electronic Journal (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
Funders
  • National Institute of Neurological Disorders and Stroke (R01NS110859)
  • Office of Research Infrastructure Programs, National Institutes of Health
  • National Institutes of Health (U54NS093793, P40OD018537)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD083092)
  • Warren Alpert Foundation (NRF-2021R1A6A3A14044510)
  • National Multiple Sclerosis Society (RG-1907-34551)
  • Howard Hughes Medical Institute
  • National Research Foundation of Korea (- 2021R1A6A3A14044510)
  • Indiana University
  • Harvard Medical School
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Keywords
very long chain fatty acids, sphingosine-1-phosphate, glial metabolism, neuroinflammation, NF-κB activation, macrophage infiltration, fingolimod, bezafibrate, experimental autoimmune encephalitis, multiple sclerosis, myelin, demyelination, fatty acid toxicity, synergistic therapy
MeSH terms
Fingolimod Hydrochloride, Neuroinflammatory Diseases, Animals, Bezafibrate, Encephalomyelitis, Autoimmune, Experimental, Fatty Acids, Immunosuppressive Agents, Lysophospholipids, Multiple Sclerosis, Neuroglia, Propylene Glycols, Sphingosine, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review