CoChat
Sign Up
Cited by 31

The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.

Balancing cholesterol in the brain: from synthesis to disposal

Qian, Lydia, Chai, Amanda B., Gelissen, Ingrid C., Brown, Andrew J.·2022·Exploration of Neuroprotective Therapy
DOI 10.37349/ent.2022.00015
Open this paper in CoChat — free account

Abstract

The cholesterol is a vital component of cell membranes and myelin sheaths, and a precursor for essential molecules such as steroid hormones. In humans, cholesterol is partially obtained through the diet, while the majority is synthesized in the body, primarily in the liver. However, the limited exchange between the central nervous system and peripheral circulation, due to the presence of the blood-brain barrier, necessitates cholesterol in the brain to be exclusively acquired from local de novo synthesis. This cholesterol is reutilized efficiently, rendering a much slower overall turnover of the compound in the brain as compared with the periphery. Furthermore, brain cholesterol is regulated independently from peripheral cholesterol. Numerous enzymes, proteins, and other factors are involved in cholesterol synthesis and metabolism in the brain. Understanding the unique mechanisms and pathways involved in the maintenance of cholesterol homeostasis in the brain is critical, considering perturbations to these processes are implicated in numerous neurodegenerative diseases. This review focuses on the developing understanding of cholesterol metabolism in the brain, discussing the sites and processes involved in its synthesis and regulation, as well as the mechanisms involved in its distribution throughout, and elimination from, the brain.

Overview

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 · 10.37349/ent.2022.00015

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Verification

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?

  • The Bloch pathway generally appears as typical for astrocytes, while microglia cells seem to preferentially resort to the Kandutsch-Russell pathway.

    “while the Bloch pathway generally appears as typical for astrocytes, microglia cells seem to preferentially resort to the Kandutsch–Russell pathway; thus, the shift to this enzymatic cascade might reflect a sort of astrocyte polarization to a cell-type more specialized in immune responses [53].”

    From ApoE3 vs. ApoE4 Astrocytes: A Detailed Analysis Provides New Insights into Differences in Cholesterol Homeostasis (2022) · cites this paper as [53]

  • The shift to the Kandutsch-Russell pathway might reflect a sort of astrocyte polarization to a cell-type more specialized in immune responses.

    “while the Bloch pathway generally appears as typical for astrocytes, microglia cells seem to preferentially resort to the Kandutsch–Russell pathway; thus, the shift to this enzymatic cascade might reflect a sort of astrocyte polarization to a cell-type more specialized in immune responses [53].”

    From ApoE3 vs. ApoE4 Astrocytes: A Detailed Analysis Provides New Insights into Differences in Cholesterol Homeostasis (2022) · cites this paper as [53]

Self-check

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

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

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 178

  1. Björkhem I, Meaney S. Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol. 2004;24:806-15. · DOI · Paper page
  2. Allen JA, Halverson-Tamboli RA, Rasenick MM. Lipid raft microdomains and neurotransmitter signalling. Nat Rev Neurosci. 2007;8:128-40. · DOI
  3. Gamba P, Staurenghi E, Testa G, Giannelli S, Sottero B, Leonarduzzi G. A crosstalk between brain cholesterol oxidation and glucose metabolism in Alzheimer’s disease. Front Neurosci. 2019;13:556. · DOI
  4. Krause MR, Regen SL. The structural role of cholesterol in cell membranes: from condensed bilayers to lipid rafts. Acc Chem Res. 2014;47:3512-21. · DOI
  5. Luu W, Sharpe LJ, Capell-Hattam I, Gelissen IC, Brown AJ. Oxysterols: old tale, new twists. Annu Rev Pharmacol Toxicol. 2016;56:447-67. · DOI
  6. Björkhem I. Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med. 2006;260:493-508. · DOI
  7. Yang J, Wang L, Jia R. Role of de novo cholesterol synthesis enzymes in cancer. J Cancer. 2020;11:1761-7. · DOI
  8. Liu M, Kuhel DG, Shen L, Hui DY, Woods SC. Apolipoprotein E does not cross the blood-cerebrospinal fluid barrier, as revealed by an improved technique for sampling CSF from mice. Am J Physiol Regul Integr Comp Physiol. 2012;303:R903-8. · DOI
  9. Quan G, Xie C, Dietschy JM, Turley SD. Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse. Brain Res Dev Brain Res. 2003;146:87-98. · DOI · Paper page
  10. Andersson M, Elmberger PG, Edlund C, Kristensson K, Dallner G. Rates of cholesterol, ubiquinone, dolichol and dolichyl-P biosynthesis in rat brain slices. FEBS Lett. 1990;269:15-8. · DOI
  11. Zhang J, Liu Q. Cholesterol metabolism and homeostasis in the brain. Protein Cell. 2015;6:254-64. · DOI · Paper page
  12. Valenza M, Marullo M, Di Paolo E, Cesana E, Zuccato C, Biella G, et al. Disruption of astrocyte-neuron cholesterol cross talk affects neuronal function in Huntington’s disease. Cell Death Differ. 2015;22:690-702. · DOI · Paper page
  13. Gill S, Stevenson J, Kristiana I, Brown AJ. Cholesterol-dependent degradation of squalene monooxygenase, a control point in cholesterol synthesis beyond HMG-CoA reductase. Cell Metab. 2011;13:260-73. · DOI · Paper page
  14. Brown MS, Radhakrishnan A, Goldstein JL. Retrospective on cholesterol homeostasis: the central role of scap. Annu Rev Biochem. 2018;87:783-807. · DOI · Paper page
  15. Courtney R, Landreth GE. LXR regulation of brain cholesterol: from development to disease. Trends Endocrinol Metab. 2016;27:404-14. · DOI · Paper page
  16. Sharpe LJ, Coates HW, Brown AJ. Post-translational control of the long and winding road to cholesterol. J Biol Chem. 2020;295:17549-59. · DOI
  17. Engelking LJ, Cantoria MJ, Xu Y, Liang G. Developmental and extrahepatic physiological functions of SREBP pathway genes in mice. Semin Cell Dev Biol. 2018;81:98-109. · DOI
  18. Nowaczyk MJM, Irons MB. Smith-Lemli-Opitz syndrome: phenotype, natural history, and epidemiology. Am J Med Genet C Semin Med Genet. 2012;160C:250-62. · DOI
  19. Pineda-Torra I, Siddique S, Waddington KE, Farrell R, Jury EC. Disrupted lipid metabolism in multiple sclerosis: a role for liver X receptors? Front Endocrinol (Lausanne). 2021;12:639757. · DOI
  20. Saito M, Benson EP, Saito M, Rosenberg A. Metabolism of cholesterol and triacylglycerol in cultured chick neuronal cells, glial cells, and fibroblasts: accumulation of esterified cholesterol in serum-free culture. J Neurosci Res. 1987;18:319-25. · DOI
  21. Nieweg K, Schaller H, Pfrieger FW. Marked differences in cholesterol synthesis between neurons and glial cells from postnatal rats. J Neurochem. 2009;109:125-34. · DOI · Paper page
  22. van Deijk AF, Camargo N, Timmerman J, Heistek T, Brouwers JF, Mogavero F, et al. Astrocyte lipid metabolism is critical for synapse development and function in vivo. Glia. 2017;65:670-82. · DOI · Paper page
  23. Tracey TJ, Steyn FJ, Wolvetang EJ, Ngo ST. Neuronal lipid metabolism: multiple pathways driving functional outcomes in health and disease. Front Mol Neurosci. 2018;11:10. · DOI
  24. Saito K, Dubreuil V, Arai Y, Wilsch-Bräuninger M, Schwudke D, Saher G, et al. Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis. Proc Natl Acad Sci U S A. 2009;106:8350-5. · DOI · Paper page
  25. Fünfschilling U, Saher G, Xiao L, Möbius W, Nave KA. Survival of adult neurons lacking cholesterol synthesis in vivo. BMC Neurosci. 2007;8:1. · DOI · Paper page
  26. Lee JA, Hall B, Allsop J, Alqarni R, Allen SP. Lipid metabolism in astrocytic structure and function. Semin Cell Dev Biol. 2021;112:123-36. · DOI · Paper page
  27. Barber CN, Raben DM. Lipid metabolism crosstalk in the brain: glia and neurons. Front Cell Neurosci. 2019;13:212. · DOI · Paper page
  28. Muse ED, Jurevics H, Toews AD, Matsushima GK, Morell P. Parameters related to lipid metabolism as markers of myelination in mouse brain. J Neurochem. 2001;76:77-86. · DOI
  29. Saher G, Stumpf SK. Cholesterol in myelin biogenesis and hypomyelinating disorders. Biochim Biophys Acta. 2015;1851:1083-94. · DOI · Paper page
  30. Williamson JM, Lyons DA. Myelin dynamics throughout life: an ever-changing landscape? Front Cell Neurosci. 2018;12:424. · DOI
  31. Werkman IL, Kövilein J, de Jonge JC, Baron W. Impairing committed cholesterol biosynthesis in white matter astrocytes, but not grey matter astrocytes, enhances in vitro myelination. J Neurochem. 2021;156:624-41. · DOI
  32. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, et al. Synaptic pruning by microglia is necessary for normal brain development. Science. 2011;333:1456-8. · DOI · Paper page
  33. Berghoff SA, Spieth L, Sun T, Hosang L, Schlaphoff L, Depp C, et al. Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis. Nat Neurosci. 2021;24:47-60. · DOI · Paper page
  34. Valdez CM, Smith MA, Perry G, Phelix CF, Santamaria F. Cholesterol homeostasis markers are localized to mouse hippocampal pyramidal and granule layers. Hippocampus. 2010;20:902-5. · DOI
  35. Pfrieger FW. Outsourcing in the brain: do neurons depend on cholesterol delivery by astrocytes? Bioessays. 2003;25:72-8. · DOI · Paper page
  36. Ohashi K, Osuga J, Tozawa R, Kitamine T, Yagyu H, Sekiya M, et al. Early embryonic lethality caused by targeted disruption of the 3-hydroxy-3-methylglutaryl-CoA reductase gene. J Biol Chem. 2003;278:42936-41. · DOI
  37. Tozawa R, Ishibashi S, Osuga J, Yagyu H, Oka T, Chen Z, et al. Embryonic lethality and defective neural tube closure in mice lacking squalene synthase. J Biol Chem. 1999;274:30843-8. · DOI
  38. Vejux A, Ghzaiel I, Nury T, Schneider V, Charrière K, Sghaier R, et al. Oxysterols and multiple sclerosis: physiopathology, evolutive biomarkers and therapeutic strategy. J Steroid Biochem Mol Biol. 2021;210:105870. · DOI
  39. Cantuti-Castelvetri L, Fitzner D, Bosch-Queralt M, Weil MT, Su M, Sen P, et al. Defective cholesterol clearance limits remyelination in the aged central nervous system. Science. 2018;359:684-8. · DOI · Paper page
  40. Chen J, Zhang X, Kusumo H, Costa LG, Guizzetti M. Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis. Biochim Biophys Acta. 2013;1831:263-75. · DOI · Paper page
  41. Mauch DH, Nägler K, Schumacher S, Göritz C, Müller EC, Otto A, et al. CNS synaptogenesis promoted by glia-derived cholesterol. Science. 2001;294:1354-7. · DOI · Paper page
  42. Flowers SA, Rebeck GW. APOE in the normal brain. Neurobiol Dis. 2020;136:104724. · DOI · Paper page
  43. Frieden C, Garai K. Structural differences between apoE3 and apoE4 may be useful in developing therapeutic agents for Alzheimer’s disease. Proc Natl Acad Sci U S A. 2012;109:8913-8. · DOI · Paper page
  44. Frieden C, Wang H, Ho CMW. A mechanism for lipid binding to apoE and the role of intrinsically disordered regions coupled to domain-domain interactions. Proc Natl Acad Sci U S A. 2017;114:6292-7. · DOI · Paper page
  45. Garai K, Baban B, Frieden C. Self-association and stability of the ApoE isoforms at low pH: implications for ApoE-lipid interactions. Biochemistry. 2011;50:6356-64. · DOI
  46. Chen J, Li Q, Wang J. Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions. Proc Natl Acad Sci U S A. 2011;108:14813-8. · DOI · Paper page
  47. Dong HK, Gim JA, Yeo SH, Kim HS. Integrated late onset Alzheimer’s disease (LOAD) susceptibility genes: cholesterol metabolism and trafficking perspectives. Gene. 2017;597:10-6. · DOI
  48. Rodríguez-Rivera C, Garcia MM, Molina-Alvarez M, González-Martín C, Goicoechea C. Clusterin: always protecting. Synthesis, function and potential issues. Biomed Pharmacother. 2021;134:111174. · DOI
  49. Artemaki PI, Sklirou AD, Kontos CK, Liosi AA, Gianniou DD, Papadopoulos IN, et al. High clusterin (CLU) mRNA expression levels in tumors of colorectal cancer patients predict a poor prognostic outcome. Clin Biochem. 2020;75:62-9. · DOI
  50. Ding X, Zhang W, Li S, Yang H. The role of cholesterol metabolism in cancer. Am J Cancer Res. 2019;9:219-27.
  51. Debure L, Vayssiere JL, Rincheval V, Loison F, Le Drean Y, Michel D. Intracellular clusterin causes juxtanuclear aggregate formation and mitochondrial alteration. J Cell Sci. 2003;116:3109-21. · DOI
  52. Herring SK, Moon HJ, Rawal P, Chhibber A, Zhao L. Brain clusterin protein isoforms and mitochondrial localization. Elife. 2019;8:e48255. · DOI
  53. Vance JE, Hayashi H. Formation and function of apolipoprotein E-containing lipoproteins in the nervous system. Biochim Biophys Acta. 2010;1801:806-18. · DOI · Paper page
  54. Gil SY, Youn BS, Byun K, Huang H, Namkoong C, Jang PG, et al. Clusterin and LRP2 are critical components of the hypothalamic feeding regulatory pathway. Nat Commun. 2013;4:1862. · DOI
  55. Elliott DA, Weickert CS, Garner B. Apolipoproteins in the brain: implications for neurological and psychiatric disorders. Clin Lipidol. 2010;51:555-73. · DOI · Paper page
  56. Orth M, Bellosta S. Cholesterol: its regulation and role in central nervous system disorders. Cholesterol. 2012;2012:292598. · DOI · Paper page
  57. Strittmatter WJ, Weisgraber KH, Huang DY, Dong LM, Salvesen GS, Pericak-Vance M, et al. Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. Proc Natl Acad Sci U S A. 1993;90:8098-102. · DOI · Paper page
  58. Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, et al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer’s disease. Proc Natl Acad Sci U S A. 2004;101:2070-5. · DOI · Paper page
  59. Xiong H, Callaghan D, Jones A, Walker DG, Lue LF, Beach TG, et al. Cholesterol retention in Alzheimer’s brain is responsible for high beta- and gamma-secretase activities and Abeta production. Neurobiol Dis. 2008;29:422-37. · DOI
  60. Chai AB, Lam HHJ, Kockx M, Gelissen IC. Apolipoprotein E isoform-dependent effects on the processing of Alzheimer’s amyloid-β. Biochim Biophys Acta Mol Cell Biol Lipids. 2021;1866:158980. · DOI
  61. Wyatt AR, Yerbury JJ, Berghofer P, Greguric I, Katsifis A, Dobson CM, et al. Clusterin facilitates in vivo clearance of extracellular misfolded proteins. Cell Mol Life Sci. 2011;68:3919-31. · DOI · Paper page
  62. Su H, Rustam YH, Masters CL, Makalic E, McLean CA, Hill AF, et al. Characterization of brain-derived extracellular vesicle lipids in Alzheimer’s disease. J Extracell Vesicles. 2021;10:e12089. · DOI
  63. Wilkens S. Structure and mechanism of ABC transporters. F1000Prime Rep. 2015;7:14. · DOI
  64. Kim WS, Guillemin GJ, Glaros EN, Lim CK, Garner B. Quantitation of ATP-binding cassette subfamily-A transporter gene expression in primary human brain cells. Neuroreport. 2006;17:891-6. · DOI
  65. Kim WS, Rahmanto AS, Kamili A, Rye KA, Guillemin GJ, Gelissen IC, et al. Role of ABCG1 and ABCA1 in regulation of neuronal cholesterol efflux to apolipoprotein E discs and suppression of amyloid-beta peptide generation. J Biol Chem. 2007;282:2851-61. · DOI · Paper page
  66. Kim WS, Weickert CS, Garner B. Role of ATP-binding cassette transporters in brain lipid transport and neurological disease. J Neurochem. 2008;104:1145-66. · DOI
  67. Fujiyoshi M, Ohtsuki S, Hori S, Tachikawa M, Terasaki T. 24S-hydroxycholesterol induces cholesterol release from choroid plexus epithelial cells in an apical- and apoE isoform-dependent manner concomitantly with the induction of ABCA1 and ABCG1 expression. J Neurochem. 2007;100:968-78. · DOI · Paper page
  68. Hartz AMS, Bauer B. ABC transporters in the CNS—an inventory. Curr Pharm Biotechnol. 2011;12:656-73. · DOI
  69. Lin T, Islam O, Heese K. ABC transporters, neural stem cells and neurogenesis—a different perspective. Cell Res. 2006;16:857-71. · DOI
  70. Vaughan AM, Oram JF. ABCA1 and ABCG1 or ABCG4 act sequentially to remove cellular cholesterol and generate cholesterol-rich HDL. J Lipid Res. 2006;47:2433-43. · DOI
  71. Matsuda A, Nagao K, Matsuo M, Kioka N, Ueda K. 24(S)-hydroxycholesterol is actively eliminated from neuronal cells by ABCA1. J Neurochem. 2013;126:93-101. · DOI
  72. Oram JF. HDL apolipoproteins and ABCA1: partners in the removal of excess cellular cholesterol. Arterioscler Thromb Vasc Biol. 2003;23:720-7. · DOI
  73. Warren MS, Zerangue N, Woodford K, Roberts LM, Tate EH, Feng B, et al. Comparative gene expression profiles of ABC transporters in brain microvessel endothelial cells and brain in five species including human. Pharmacol Res. 2009;59:404-13. · DOI
  74. Sakai H, Tanaka Y, Tanaka M, Ban N, Yamada K, Matsumura Y, et al. ABCA2 deficiency results in abnormal sphingolipid metabolism in mouse brain. J Biol Chem. 2007;282:19692-9. · DOI
  75. Calpe-Berdiel L, Zhao Y, de Graauw M, Ye D, van Santbrink PJ, Mommaas AM, et al. Macrophage ABCA2 deletion modulates intracellular cholesterol deposition, affects macrophage apoptosis, and decreases early atherosclerosis in LDL receptor knockout mice. Atherosclerosis. 2012;223:332-41. · DOI
  76. Davis W Jr. The ATP-binding cassette transporter-2 (ABCA2) regulates cholesterol homeostasis and low-density lipoprotein receptor metabolism in N2a neuroblastoma cells. Biochim Biophys Acta. 2011;1811:1152-64. · DOI
  77. Ban N, Matsumura Y, Sakai H, Takanezawa Y, Sasaki M, Arai H, et al. ABCA3 as a lipid transporter in pulmonary surfactant biogenesis. J Biol Chem. 2007;282:9628-34. · DOI
  78. Fitzgerald ML, Xavier R, Haley KJ, Welti R, Goss JL, Brown CE, et al. ABCA3 inactivation in mice causes respiratory failure, loss of pulmonary surfactant, and depletion of lung phosphatidylglycerol. J Lipid Res. 2007;48:621-32. · DOI
  79. Cheong N, Madesh M, Gonzales LW, Zhao M, Yu K, Ballard PL, et al. Functional and trafficking defects in ATP binding cassette A3 mutants associated with respiratory distress syndrome. J Biol Chem. 2006;281:9791-800. · DOI
  80. Ikeda Y, Abe-Dohmae S, Munehira Y, Aoki R, Kawamoto S, Furuya A, et al. Posttranscriptional regulation of human ABCA7 and its function for the apoA-I-dependent lipid release. Biochem Biophys Res Commun. 2003;311:313-8. · DOI
  81. Wang N, Lan D, Gerbod-Giannone M, Linsel-Nitschke P, Jehle AW, Chen W, et al. ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and mediates cellular phospholipid but not cholesterol efflux. J Biol Chem. 2003;278:42906-12. · DOI
  82. Chan SL, Kim WS, Kwok JB, Hill AF, Cappai R, Rye KA, et al. ATP-binding cassette transporter A7 regulates processing of amyloid precursor protein in vitro. J Neurochem. 2008;106:793-804. · DOI
  83. Matsumoto N, Kitayama H, Kitada M, Kimura K, Noda M, Ide C. Isolation of a set of genes expressed in the choroid plexus of the mouse using suppression subtractive hybridization. Neuroscience. 2003;117:405-15. · DOI
  84. Trigueros-Motos L, van Capelleveen JC, Torta F, Castaño D, Zhang LH, Chai EC, et al. ABCA8 regulates cholesterol efflux and high-density lipoprotein cholesterol levels. Arterioscler Thromb Vasc Biol. 2017;37:2147-55. · DOI
  85. Kooij G, van Horssen J, Bandaru VV, Haughey NJ, de Vries HE. The role of ATP-binding cassette transporters in neuro-inflammation: relevance for bioactive lipids. Front Pharmacol. 2012;3:74. · DOI
  86. Mahringer A, Fricker G. ABC transporters at the blood-brain barrier. Expert Opin Drug Metab Toxicol. 2016;12:499-508. · DOI
  87. Neumann J, Rose-Sperling D, Hellmich UA. Diverse relations between ABC transporters and lipids: an overview. Biochim Biophys Acta Biomembr. 2017;1859:605-18. · DOI
  88. Pohl A, Lage H, Müller P, Pomorski T, Herrmann A. Transport of phosphatidylserine via MDR1 (multidrug resistance 1)P-glycoprotein in a human gastric carcinoma cell line. Biochem J. 2002;365:259-68. · DOI
  89. van Helvoort A, Smith AJ, Sprong H, Fritzsche I, Schinkel AH, Borst P, et al. MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell. 1996;87:507-17. · DOI
  90. Garrigues A, Escargueil AE, Orlowski S. The multidrug transporter, P-glycoprotein, actively mediates cholesterol redistribution in the cell membrane. Proc Natl Acad Sci U S A. 2002;99:10347-52. · DOI
  91. Le Goff W, Settle M, Greene DJ, Morton RE, Smith JD. Reevaluation of the role of the multidrug-resistant P-glycoprotein in cellular cholesterol homeostasis. J Lipid Res. 2006;47:51-8. · DOI
  92. Eckford PDW, Sharom FJ. The reconstituted P-glycoprotein multidrug transporter is a flippase for glucosylceramide and other simple glycosphingolipids. Biochem J. 2005;389:517-26. · DOI
  93. Beck K, Hayashi K, Dang K, Hayashi M, Boyd CD. Analysis of ABCC6 (MRP6) in normal human tissues. Histochem Cell Biol. 2005;123:517-28. · DOI
  94. Ibold B, Tiemann J, Faust I, Ceglarek U, Dittrich J, Gorgels TGMF, et al. Genetic deletion of Abcc6 disturbs cholesterol homeostasis in mice. Sci Rep. 2021;11:2137. · DOI
  95. Wang N, Yvan-Charvet L, Lütjohann D, Mulder M, Vanmierlo T, Kim TW, et al. ATP-binding cassette transporters G1 and G4 mediate cholesterol and desmosterol efflux to HDL and regulate sterol accumulation in the brain. FASEB J. 2008;22:1073-82. · DOI · Paper page
  96. Burgess BL, Parkinson PF, Racke MM, Hirsch-Reinshagen V, Fan J, Wong C, et al. ABCG1 influences the brain cholesterol biosynthetic pathway but does not affect amyloid precursor protein or apolipoprotein E metabolism in vivo. J Lipid Res. 2008;49:1254-67. · DOI
  97. Kobayashi A, Takanezawa Y, Hirata T, Shimizu Y, Misasa K, Kioka N, et al. Efflux of sphingomyelin, cholesterol, and phosphatidylcholine by ABCG1. J Lipid Res. 2006;47:1791-802. · DOI
  98. Xu M, Zhou H, Tan KCB, Guo R, Shiu SWM, Wong Y. ABCG1 mediated oxidized LDL-derived oxysterol efflux from macrophages. Biochem Biophys Res Commun. 2009;390:1349-54. · DOI
  99. Dodacki A, Wortman M, Saubaméa B, Chasseigneaux S, Nicolic S, Prince N, et al. Expression and function of Abcg4 in the mouse blood-brain barrier: role in restricting the brain entry of amyloid-β peptide. Sci Rep. 2017;7:13393. · DOI
  100. Wang N, Lan D, Chen W, Matsuura F, Tall AR. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc Natl Acad Sci U S A. 2004;101:9774-9. · DOI
  101. Bojanic DD, Tarr PT, Gale GD, Smith DJ, Bok D, Chen B, et al. Differential expression and function of ABCG1 and ABCG4 during development and aging. J Lipid Res. 2010;51:169-81. · DOI
  102. Yang A, Alrosan AZ, Sharpe LJ, Brown AJ, Callaghan R, Gelissen IC. Regulation of ABCG4 transporter expression by sterols and LXR ligands. Biochim Biophys Acta Gen Subj. 2021;1865:129769. · DOI
  103. Gelissen IC, Harris M, Rye KA, Quinn C, Brown AJ, Kockx M, et al. ABCA1 and ABCG1 synergize to mediate cholesterol export to apoA-I. Arterioscler Thromb Vasc Biol. 2006;26:534-40. · DOI
  104. Hirsch-Reinshagen V, Zhou S, Burgess BL, Bernier L, McIsaac SA, Chan JY, et al. Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain. J Biol Chem. 2004;279:41197-207. · DOI · Paper page
  105. Karten B, Campenot RB, Vance DE, Vance JE. Expression of ABCG1, but not ABCA1, correlates with cholesterol release by cerebellar astroglia. J Biol Chem. 2006;281:4049-57. · DOI · Paper page
  106. Oram JF, Lawn RM. ABCA1: the gatekeeper for eliminating excess tissue cholesterol. J Lipid Res. 2001;42:1173-9. · DOI
  107. Karasinska JM, Rinninger F, Lütjohann D, Ruddle P, Franciosi S, Kruit JK, et al. Specific loss of brain ABCA1 increases brain cholesterol uptake and influences neuronal structure and function. J Neurosci. 2009;29:3579-89. · DOI · Paper page
  108. Wahrle SE, Jiang H, Parsadanian M, Legleiter J, Han X, Fryer JD, et al. ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE. J Biol Chem. 2004;279:40987-93. · DOI · Paper page
  109. Davis W Jr. The ATP-binding cassette transporter-2 (ABCA2) regulates esterification of plasma membrane cholesterol by modulation of sphingolipid metabolism. Biochim Biophys Acta. 2014; 1841:168-79. · DOI
  110. De Roeck A, Van Broeckhoven C, Sleegers K. The role of ABCA7 in Alzheimer’s disease: evidence from genomics, transcriptomics and methylomics. Acta Neuropathol. 2019;138:201-20. · DOI · Paper page
  111. Lyssenko NN, Praticò D. ABCA7 and the altered lipidostasis hypothesis of Alzheimer’s disease. Alzheimers Dement. 2021;17:164-74. · DOI
  112. Dib S, Pahnke J, Gosselet F. Role of ABCA7 in human health and in Alzheimer’s disease. Int J Mol Sci. 2021;22:4603. · DOI
  113. Steinberg S, Stefansson H, Jonsson T, Johannsdottir H, Ingason A, Helgason H, et al. Loss-of-function variants in ABCA7 confer risk of Alzheimer’s disease. Nat Genet. 2015;47:445-7. · DOI · Paper page
  114. Kim WS, Hsiao JH, Bhatia S, Glaros EN, Don AS, Tsuruoka S, et al. ABCA8 stimulates sphingomyelin production in oligodendrocytes. Biochem J. 2013;452:401-10. · DOI
  115. Brampton C, Pomozi V, Chen LH, Apana A, McCurdy S, Zoll J, et al. ABCC6 deficiency promotes dyslipidemia and atherosclerosis. Sci Rep. 2021;11:3881. · DOI
  116. Kuzaj P, Kuhn J, Dabisch-Ruthe M, Faust I, Götting C, Knabbe C, et al. ABCC6-a new player in cellular cholesterol and lipoprotein metabolism? Lipids Health Dis. 2014;13:118. · DOI
  117. Cserepes J, Szentpétery Z, Seres L, Ozvegy-Laczka C, Langmann T, Schmitz G, et al. Functional expression and characterization of the human ABCG1 and ABCG4 proteins: indications for heterodimerization. Biochem Biophys Res Commun. 2004;320:860-7. · DOI
  118. Tarr PT, Edwards PA. ABCG1 and ABCG4 are coexpressed in neurons and astrocytes of the CNS and regulate cholesterol homeostasis through SREBP-2. J Lipid Res. 2008;49:169-82. · DOI
  119. DeBose-Boyd RA, Ye J. SREBPs in lipid metabolism, insulin signaling, and beyond. Trends Biochem Sci. 2018;43:358-68. · DOI
  120. Mitchell KJ, Pinson KI, Kelly OG, Brennan J, Zupicich J, Scherz P, et al. Functional analysis of secreted and transmembrane proteins critical to mouse development. Nat Genet. 2001;28:241-9. · DOI · Paper page
  121. Shimano H, Shimomura I, Hammer RE, Herz J, Goldstein JL, Brown MS, et al. Elevated levels of SREBP-2 and cholesterol synthesis in livers of mice homozygous for a targeted disruption of the SREBP-1 gene. J Clin Invest. 1997;100:2115-24. · DOI · Paper page
  122. Engelking LJ, Evers BM, Richardson JA, Goldstein JL, Brown MS, Liang G. Severe facial clefting in Insig-deficient mouse embryos caused by sterol accumulation and reversed by lovastatin. J Clin Invest. 2006;116:2356-65. · DOI · Paper page
  123. Suzuki R, Ferris HA, Chee MJ, Maratos-Flier E, Kahn CR. Reduction of the cholesterol sensor SCAP in the brains of mice causes impaired synaptic transmission and altered cognitive function. PLoS Biol. 2013;11:e1001532. · DOI
  124. Camargo N, Brouwers JF, Loos M, Gutmann DH, Smit AB, Verheijen MHG. High-fat diet ameliorates neurological deficits caused by defective astrocyte lipid metabolism. FASEB J. 2012;26:4302-15. · DOI
  125. Engelking LJ, Liang G, Hammer RE, Takaishi K, Kuriyama H, Evers BM, et al. Schoenheimer effect explained—feedback regulation of cholesterol synthesis in mice mediated by Insig proteins. J Clin Invest. 2005;115:2489-98. · DOI · Paper page
  126. Hwang S, Nguyen AD, Jo Y, Engelking LJ, Brugarolas J, DeBose-Boyd RA. Hypoxia-inducible factor 1α activates insulin-induced gene 2 (Insig-2) transcription for degradation of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase in the liver. J Biol Chem. 2017;292:9382-93. · DOI
  127. Plantier L, Besnard V, Xu Y, Ikegami M, Wert SE, Hunt AN, et al. Activation of sterol-response element-binding proteins (SREBP) in alveolar type II cells enhances lipogenesis causing pulmonary lipotoxicity. J Biol Chem. 2012;287:10099-114. · DOI
  128. Bilotta MT, Petillo S, Santoni A, Cippitelli M. Liver X receptors: regulators of cholesterol metabolism, inflammation, autoimmunity, and cancer. Front Immunol. 2020;11:584303. · DOI
  129. Wang L, Schuster GU, Hultenby K, Zhang Q, Andersson S, Gustafsson JA. Liver X receptors in the central nervous system: from lipid homeostasis to neuronal degeneration. Proc Natl Acad Sci U S A. 2002;99:13878-83. · DOI
  130. Widenmaier SB, Snyder NA, Nguyen TB, Arduini A, Lee GY, Arruda AP, et al. NRF1 is an ER membrane sensor that is central to cholesterol homeostasis. Cell. 2017;171:1094-109.e15. · DOI
  131. Lee CS, Lee C, Hu T, Nguyen JM, Zhang J, Martin MV, et al. Loss of nuclear factor E2-related factor 1 in the brain leads to dysregulation of proteasome gene expression and neurodegeneration. Proc Natl Acad Sci U S A. 2011;108:8408-13. · DOI
  132. Rahimi-Balaei M, Bergen H, Kong J, Marzban H. Neuronal migration during development of the cerebellum. Front Cell Neurosci. 2018;12:484. · DOI
  133. Fan X, Kim HJ, Bouton D, Warner M, Gustafsson JA. Expression of liver X receptor beta is essential for formation of superficial cortical layers and migration of later-born neurons. Proc Natl Acad Sci U S A. 2008;105:13445-50. · DOI · Paper page
  134. Do HT, Bruelle C, Tselykh T, Jalonen P, Korhonen L, Lindholm D. Reciprocal regulation of very low density lipoprotein receptors (VLDLRs) in neurons by brain-derived neurotrophic factor (BDNF) and Reelin: involvement of the E3 ligase Mylip/Idol. J Biol Chem. 2013;288:29613-20. · DOI · Paper page
  135. Hirota Y, Kubo K, Katayama K, Honda T, Fujino T, Yamamoto TT, et al. Reelin receptors ApoER2 and VLDLR are expressed in distinct spatiotemporal patterns in developing mouse cerebral cortex. J Comp Neurol. 2015;523:463-78. · DOI
  136. Sakashita N, Miyazaki A, Takeya M, Horiuchi S, Chang CC, Chang TY, et al. Localization of human acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) in macrophages and in various tissues. Am J Pathol. 2000;156:227-36. · DOI
  137. Chang TY, Chang CCY, Bryleva E, Rogers MA, Murphy SR. Neuronal cholesterol esterification by ACAT1 in Alzheimer’s disease. IUBMB Life. 2010;62:261-7. · DOI
  138. Pitas RE, Boyles JK, Lee SH, Hui D, Weisgraber KH. Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain. J Biol Chem. 1987;262:14352-60. · DOI · Paper page
  139. Mahley RW. Central nervous system lipoproteins: ApoE and regulation of cholesterol metabolism. Arterioscler Thromb Vasc Biol. 2016;36:1305-15. · DOI · Paper page
  140. Do TM, Ouellet M, Calon F, Chimini G, Chacun H, Farinotti R, et al. Direct evidence of abca1-mediated efflux of cholesterol at the mouse blood-brain barrier. Mol Cell Biochem. 2011;357:397-404. · DOI · Paper page
  141. Pifferi F, Laurent B, Plourde M. Lipid transport and metabolism at the blood-brain interface: implications in health and disease. Front Physiol. 2021;12:645646. · DOI · Paper page
  142. Saeed AA, Genové G, Li T, Lütjohann D, Olin M, Mast N, et al. Effects of a disrupted blood-brain barrier on cholesterol homeostasis in the brain. J Biol Chem. 2014;289:23712-22. · DOI
  143. Björkhem I, Lütjohann D, Breuer O, Sakinis A, Wennmalm A. Importance of a novel oxidative mechanism for elimination of brain cholesterol. Turnover of cholesterol and 24(S)-hydroxycholesterol in rat brain as measured with 18O techniques in vivo and in vitro. J Biol Chem. 1997;272:30178-84. · DOI
  144. Lund EG, Guileyardo JM, Russell DW. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc Natl Acad Sci U S A. 1999;96:7238-43. · DOI · Paper page
  145. Ramirez DMO, Andersson S, Russell DW. Neuronal expression and subcellular localization of cholesterol 24-hydroxylase in the mouse brain. J Comp Neurol. 2008;507:1676-93. · DOI
  146. Bogdanovic N, Bretillon L, Lund EG, Diczfalusy U, Lannfelt L, Winblad B, et al. On the turnover of brain cholesterol in patients with Alzheimer’s disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells. Neurosci Lett. 2001;314:45-8. · DOI
  147. Cartagena CM, Ahmed F, Burns MP, Pajoohesh-Ganji A, Pak DT, Faden AI, et al. Cortical injury increases cholesterol 24S hydroxylase (Cyp46) levels in the rat brain. J Neurotrauma. 2008;25:1087-98. · DOI
  148. Smiljanic K, Lavrnja I, Mladenovic Djordjevic A, Ruzdijic S, Stojiljkovic M, Pekovic S, et al. Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner. Histochem Cell Biol. 2010;134:159-69. · DOI
  149. Tian G, Kong Q, Lai L, Ray-Chaudhury A, Lin CLG. Increased expression of cholesterol 24S-hydroxylase results in disruption of glial glutamate transporter EAAT2 association with lipid rafts: a potential role in Alzheimer’s disease. J Neurochem. 2010;113:978-89. · DOI
  150. Lütjohann D, Breuer O, Ahlborg G, Nennesmo I, Sidén A, Diczfalusy U, et al. Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc Natl Acad Sci U S A. 1996;93:9799-804. · DOI · Paper page
  151. Ohtsuki S, Ito S, Matsuda A, Hori S, Abe T, Terasaki T. Brain-to-blood elimination of 24S-hydroxycholesterol from rat brain is mediated by organic anion transporting polypeptide 2 (oatp2) at the blood-brain barrier. J Neurochem. 2007;103:1430-8. · DOI
  152. Björkhem I, Lütjohann D, Diczfalusy U, Ståhle L, Ahlborg G, Wahren J. Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res. 1998;39:1594-600. · DOI · Paper page
  153. Bretillon L, Lütjohann D, Ståhle L, Widhe T, Bindl L, Eggertsen G, et al. Plasma levels of 24S-hydroxycholesterol reflect the balance between cerebral production and hepatic metabolism and are inversely related to body surface. J Lipid Res. 2000;41:840-5. · DOI
  154. Kim WS, Chan SL, Hill AF, Guillemin GJ, Garner B. Impact of 27-hydroxycholesterol on amyloid-beta peptide production and ATP-binding cassette transporter expression in primary human neurons. J Alzheimers Dis. 2009;16:121-31. · DOI
  155. Moutinho M, Nunes MJ, Gomes AQ, Gama MJ, Cedazo-Minguez A, Rodrigues CM, et al. Cholesterol 24S-hydroxylase overexpression inhibits the liver X receptor (LXR) pathway by activating small guanosine triphosphate-binding proteins (sGTPases) in neuronal cells. Mol Neurobiol. 2015;51:1489-503. · DOI
  156. Noguchi N, Saito Y, Urano Y. Diverse functions of 24(S)-hydroxycholesterol in the brain. Biochem Biophys Res Commun. 2014;446:692-6. · DOI
  157. Brown AJ, Sharpe LJ, Rogers MJ. Oxysterols: from physiological tuners to pharmacological opportunities. Br J Pharmacol. 2021;178:3089-103. · DOI
  158. Qi X, Liu H, Thompson B, McDonald J, Zhang C, Li X. Cryo-EM structure of oxysterol-bound human Smoothened coupled to a heterotrimeric G . Nature. 2019;571:279-83. · DOI
  159. Zhornitsky S, McKay KA, Metz LM, Teunissen CE, Rangachari M. Cholesterol and markers of cholesterol turnover in multiple sclerosis: relationship with disease outcomes. Mult Scler Relat Disord. 2016;5:53-65. · DOI
  160. Han M, Wang S, Yang N, Wang X, Zhao W, Saed HS, et al. Therapeutic implications of altered cholesterol homeostasis mediated by loss of CYP46A1 in human glioblastoma. EMBO Mol Med. 2020;12:e10924. · DOI
  161. Wang Y, Muneton S, Sjövall J, Jovanovic JN, Griffiths WJ. The effect of 24S-hydroxycholesterol on cholesterol homeostasis in neurons: quantitative changes to the cortical neuron proteome. J Proteome Res. 2008;7:1606-14. · DOI
  162. Gamba P, Giannelli S, Staurenghi E, Testa G, Sottero B, Biasi F, et al. The controversial role of 24-S-hydroxycholesterol in Alzheimer’s disease. Antioxidants (Basel). 2021;10:740. · DOI · Paper page
  163. Sodero AO. 24S-hydroxycholesterol: cellular effects and variations in brain diseases. J Neurochem. 2021;157:899-918. · DOI
  164. Yamanaka K, Saito Y, Yamamori T, Urano Y, Noguchi N. 24(S)-hydroxycholesterol induces neuronal cell death through necroptosis, a form of programmed necrosis. J Biol Chem. 2011;286:24666-73. · DOI
  165. Zarrouk A, Hammami M, Moreau T, Lizard G. Accumulation of 24S-hydroxycholesterol in neuronal SK-N-BE cells treated with hexacosanoic acid (C26:0): argument in favor of 24S-hydroxycholesterol as a potential biomarker of neurolipotoxicity. Rev Neurol (Paris). 2015;171:125-9. · DOI
  166. Björkhem I, Leoni V, Svenningsson P. On the fluxes of side-chain oxidized oxysterols across blood-brain and blood-CSF barriers and origin of these steroids in CSF (review). J Steroid Biochem Mol Biol. 2019;188:86-9. · DOI · Paper page
  167. Heverin M, Meaney S, Lütjohann D, Diczfalusy U, Wahren J, Björkhem I. Crossing the barrier: net flux of 27-hydroxycholesterol into the human brain. J Lipid Res. 2005;46:1047-52. · DOI
  168. Zhang DD, Yu HL, Ma WW, Liu QR, Han J, Wang H, et al. 27-Hydroxycholesterol contributes to disruptive effects on learning and memory by modulating cholesterol metabolism in the rat brain. Neuroscience. 2015;300:163-73. · DOI
  169. Spencer TA, Gayen AK, Phirwa S, Nelson JA, Taylor FR, Kandutsch AA, et al. 24(S),25-Epoxycholesterol. Evidence consistent with a role in the regulation of hepatic cholesterogenesis. J Biol Chem. 1985;260:13391-4. · DOI
  170. Goyal S, Xiao Y, Porter NA, Xu L, Guengerich FP. Oxidation of 7-dehydrocholesterol and desmosterol by human cytochrome P450 46A1. J Lipid Res. 2014;55:1933-43. · DOI
  171. Wong J, Quinn CM, Guillemin G, Brown AJ. Primary human astrocytes produce 24(S),25-epoxycholesterol with implications for brain cholesterol homeostasis. J Neurochem. 2007;103:1764-73. · DOI
  172. Meljon A, Theofilopoulos S, Shackleton CHL, Watson GL, Javitt NB, Knölker HJ, et al. Analysis of bioactive oxysterols in newborn mouse brain by LC/MS. J Lipid Res. 2012;53:2469-83. · DOI
  173. Hubler Z, Friedrich RM, Sax JL, Allimuthu D, Gao F, Rivera-León AM, et al. Modulation of lanosterol synthase drives 24,25-epoxysterol synthesis and oligodendrocyte formation. Cell Chem Biol. 2021;28:866-75.e5. · DOI
  174. Theofilopoulos S, Abreu de Oliveira WA, Yang S, Yutuc E, Saeed A, Abdel-Khalik J, et al. 24(S),25-Epoxycholesterol and cholesterol 24S-hydroxylase (CYP46A1) overexpression promote midbrain dopaminergic neurogenesis in vivo. J Biol Chem. 2019;294:4169-76. · DOI
  175. Roeper J. Dissecting the diversity of midbrain dopamine neurons. Trends Neurosci. 2013;36:336-42. · DOI
  176. Luo J, Yang H, Song BL. Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol. 2020;21:225-45. · DOI · Paper page
  177. Jin U, Park SJ, Park SM. Cholesterol metabolism in the brain and its association with Parkinson’s disease. Exp Neurobiol. 2019;28:554-67. · DOI · Paper page
  178. Petrov AM, Kasimov MR, Zefirov AL. Brain cholesterol metabolism and its defects: linkage to neurodegenerative diseases and synaptic dysfunction. Acta Naturae. 2016;8:58-73. · DOI

Cited by

Sorted by citations

Metadata

Authors
Qian, L., Chai, A. B., Gelissen, I. C., & Brown, A. J.
Affiliations
  • School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, New South Wales, 2052, Australia
  • School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales 2006, Australia
ORCID
Venue
Exploration of Neuroprotective Therapy
Publisher
Open Exploration Publishing
Published
2022-01-05
Pages
1-27
DOI
10.37349/ent.2022.00015
Cited by
31
References
29
Language
en
Licence
doi.org/10.37349/Open_Exploration_Crossmark_Policy (unspecified)

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