The Impact of Phytosterols on the Healthy and Diseased Brain

Author(s): Tess Dierckx, Jeroen F.J. Bogie, Jerome J.A. Hendriks*.

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 37 , 2019

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Abstract:

The central nervous system (CNS) is the most cholesterol-rich organ in mammals. Cholesterol homeostasis is essential for proper brain functioning and dysregulation of cholesterol metabolism can lead to neurological problems. Multiple sclerosis (MS) and Alzheimer’s disease (AD) are examples of neurological diseases that are characterized by a disturbed cholesterol metabolism. Phytosterols (PS) are plant-derived components that structurally and functionally resemble cholesterol. PS are known for their cholesterol-lowering properties. Due to their ability to reach the brain, researchers have started to investigate the physiological role of PS in the CNS. In this review, the metabolism and function of PS in the diseased and healthy CNS are discussed.

Keywords: Phytosterols, cholesterol, central nervous system, multiple sclerosis, Alzheimer’s disease, add-on therapy.

[1]
Ostlund, R.E. Jr. Phytosterols and cholesterol metabolism. Curr. Opin. Lipidol., 2004, 15(1), 37-41.
[http://dx.doi.org/10.1097/00041433-200402000-00008] [PMID: 15166807]
[2]
Bitzur, R.; Cohen, H.; Kamari, Y.; Harats, D. [Phytosterols: another way to reduce LDL cholesterol levels]. Harefuah, 2013, 152(12), 729-731, 751.
[PMID: 24482998]
[3]
Vanmierlo, T.; Bogie, J.F.; Mailleux, J.; Vanmol, J.; Lütjohann, D.; Mulder, M.; Hendriks, J.J. Plant sterols: Friend or foe in CNS disorders? Prog. Lipid Res., 2015, 58, 26-39.
[http://dx.doi.org/10.1016/j.plipres.2015.01.003] [PMID: 25623279]
[4]
Vanmierlo, T.; Husche, C.; Schött, H.F.; Pettersson, H.; Lütjohann, D. Plant sterol oxidation products--analogs to cholesterol oxidation products from plant origin? Biochimie, 2013, 95(3), 464-472.
[http://dx.doi.org/10.1016/j.biochi.2012.09.021] [PMID: 23009926]
[5]
Akhisa, T.; Kokke, W.; Tamura, T. Naturally occuring sterols and related compounds from plants champaign, illinois: american oil chemists' society, 1991.
[6]
Piironen, V.; Lindsay, D.G.; Miettinen, T.A.; Toivo, J.; Lampi, A-M. Plant sterols: biosynthesis, biological function and their importance to human nutrition. J. Sci. Food Agric., 2000, 80(7), 939-966.
[http://dx.doi.org/10.1002/(SICI)1097-0010(20000515)80:7<939:AID-JSFA644>3.0.CO;2-C]
[7]
Gylling, H.; Simonen, P. Phytosterols, phytostanols, and lipoprotein metabolism. Nutrients, 2015, 7(9), 7965-7977.
[http://dx.doi.org/10.3390/nu7095374] [PMID: 26393644]
[8]
Amiot, M.J.; Knol, D.; Cardinault, N.; Nowicki, M.; Bott, R.; Antona, C.; Borel, P.; Bernard, J.P.; Duchateau, G.; Lairon, D. Phytosterol ester processing in the small intestine: impact on cholesterol availability for absorption and chylomicron cholesterol incorporation in healthy humans. J. Lipid Res., 2011, 52(6), 1256-1264.
[http://dx.doi.org/10.1194/jlr.M013730] [PMID: 21482714]
[9]
Wasowicz, E. Cholesterol and phytosterol chemical and functional properties of food lipids, 2002, 93
[10]
Grandgirard, A.; Martine, L.; Joffre, C.; Juaneda, P.; Berdeaux, O. Gas chromatographic separation and mass spectrometric identification of mixtures of oxyphytosterol and oxycholesterol derivatives application to a phytosterol-enriched food. J. Chromatogr. A, 2004, 1040(2), 239-250.
[http://dx.doi.org/10.1016/j.chroma.2004.04.008] [PMID: 15230531]
[11]
Menéndez-Carreño, M.; Steenbergen, H.; Janssen, H.G. Development and validation of a comprehensive two-dimensional gas chromatography-mass spectrometry method for the analysis of phytosterol oxidation products in human plasma. Anal. Bioanal. Chem., 2012, 402(6), 2023-2032.
[http://dx.doi.org/10.1007/s00216-011-5432-2] [PMID: 21972006]
[12]
Husche, C.; Weingärtner, O.; Pettersson, H.; Vanmierlo, T.; Böhm, M.; Laufs, U.; Lütjohann, D. Validation of an isotope dilution gas chromatography-mass spectrometry method for analysis of 7-oxygenated campesterol and sitosterol in human serum. Chem. Phys. Lipids, 2011, 164(6), 425-431.
[http://dx.doi.org/10.1016/j.chemphyslip.2011.04.009] [PMID: 21620808]
[13]
Hovenkamp, E.; Demonty, I.; Plat, J.; Lütjohann, D.; Mensink, R.P.; Trautwein, E.A. Biological effects of oxidized phytosterols: a review of the current knowledge. Prog. Lipid Res., 2008, 47(1), 37-49.
[http://dx.doi.org/10.1016/j.plipres.2007.10.001] [PMID: 18022398]
[14]
Maguire, L.; Konoplyannikov, M.; Ford, A.; Maguire, A.R.; O’Brien, N.M. Comparison of the cytotoxic effects of beta-sitosterol oxides and a cholesterol oxide, 7beta-hydroxycholesterol, in cultured mammalian cells. Br. J. Nutr., 2003, 90(4), 767-775.
[http://dx.doi.org/10.1079/BJN2003956] [PMID: 13129445]
[15]
Moreau, R.A.; Whitaker, B.D.; Hicks, K.B. Phytosterols, phytostanols, and their conjugates in foods: structural diversity, quantitative analysis, and health-promoting uses. Prog. Lipid Res., 2002, 41(6), 457-500.
[http://dx.doi.org/10.1016/S0163-7827(02)00006-1] [PMID: 12169300]
[16]
Dufourc, E.J. Sterols and membrane dynamics. J. Chem. Biol., 2008, 1(1-4), 63-77.
[http://dx.doi.org/10.1007/s12154-008-0010-6] [PMID: 19568799]
[17]
Jiménez-Escrig, A.; Santos-Hidalgo, A.B.; Saura-Calixto, F. Common sources and estimated intake of plant sterols in the Spanish diet. J. Agric. Food Chem., 2006, 54(9), 3462-3471.
[http://dx.doi.org/10.1021/jf053188k] [PMID: 16637708]
[18]
Valsta, L.M.; Lemström, A.; Ovaskainen, M.L.; Lampi, A.M.; Toivo, J.; Korhonen, T.; Piironen, V. Estimation of plant sterol and cholesterol intake in Finland: quality of new values and their effect on intake. Br. J. Nutr., 2004, 92(4), 671-678.
[http://dx.doi.org/10.1079/BJN20041234] [PMID: 15522137]
[19]
Klingberg, S.; Andersson, H.; Mulligan, A.; Bhaniani, A.; Welch, A.; Bingham, S.; Khaw, K.T.; Andersson, S.; Ellegård, L. Food sources of plant sterols in the EPIC Norfolk population. Eur. J. Clin. Nutr., 2008, 62(6), 695-703.
[http://dx.doi.org/10.1038/sj.ejcn.1602765] [PMID: 17440516]
[20]
Gylling, H.; Plat, J.; Turley, S.; Ginsberg, H.N.; Ellegård, L.; Jessup, W.; Jones, P.J.; Lütjohann, D.; Maerz, W.; Masana, L.; Silbernagel, G.; Staels, B.; Borén, J.; Catapano, A.L.; De Backer, G.; Deanfield, J.; Descamps, O.S.; Kovanen, P.T.; Riccardi, G.; Tokgözoglu, L.; Chapman, M.J. European Atherosclerosis Society Consensus Panel on Phytosterols. Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atherosclerosis, 2014, 232(2), 346-360.
[http://dx.doi.org/10.1016/j.atherosclerosis.2013.11.043] [PMID: 24468148]
[21]
von Bergmann, K.; Sudhop, T.; Lütjohann, D. Cholesterol and plant sterol absorption: recent insights. Am. J. Cardiol., 2005, 96(1A), 10D-14D.
[http://dx.doi.org/10.1016/j.amjcard.2005.03.014] [PMID: 15992510]
[22]
Ostlund, R.E. Jr. Phytosterols in human nutrition. Annu. Rev. Nutr., 2002, 22, 533-549.
[http://dx.doi.org/10.1146/annurev.nutr.22.020702.075220] [PMID: 12055357]
[23]
Ling, W.H.; Jones, P.J. Dietary phytosterols: a review of metabolism, benefits and side effects. Life Sci., 1995, 57(3), 195-206.
[http://dx.doi.org/10.1016/0024-3205(95)00263-6] [PMID: 7596226]
[24]
Boberg, K.M.; Skrede, S. Content of sitosterol, cholestanol, and cholesterol in very low density lipoproteins of rat liver perfusate. Scand. J. Gastroenterol., 1988, 23(4), 442-448.
[http://dx.doi.org/10.3109/00365528809093892] [PMID: 3381065]
[25]
Eberlé, D.; Hegarty, B.; Bossard, P.; Ferré, P.; Foufelle, F. SREBP transcription factors: master regulators of lipid homeostasis. Biochimie, 2004, 86(11), 839-848.
[http://dx.doi.org/10.1016/j.biochi.2004.09.018] [PMID: 15589694]
[26]
Sun, L.P.; Li, L.; Goldstein, J.L.; Brown, M.S. Insig required for sterol-mediated inhibition of Scap/SREBP binding to COPII proteins in vitro. J. Biol. Chem., 2005, 280(28), 26483-26490.
[http://dx.doi.org/10.1074/jbc.M504041200] [PMID: 15899885]
[27]
Nohturfft, A.; Yabe, D.; Goldstein, J.L.; Brown, M.S.; Espenshade, P.J. Regulated step in cholesterol feedback localized to budding of SCAP from ER membranes. Cell, 2000, 102(3), 315-323.
[http://dx.doi.org/10.1016/S0092-8674(00)00037-4] [PMID: 10975522]
[28]
Ye, J.; DeBose-Boyd, R.A. Regulation of cholesterol and fatty acid synthesis. Cold Spring Harb. Perspect. Biol., 2011, 3(7)a004754
[http://dx.doi.org/10.1101/cshperspect.a004754] [PMID: 21504873]
[29]
Yang, C.; Yu, L.; Li, W.; Xu, F.; Cohen, J.C.; Hobbs, H.H. Disruption of cholesterol homeostasis by plant sterols. J. Clin. Invest., 2004, 114(6), 813-822.
[http://dx.doi.org/10.1172/JCI22186] [PMID: 15372105]
[30]
Shefer, S.; Salen, G.; Nguyen, L.; Batta, A.K.; Packin, V.; Tint, G.S.; Hauser, S. Competitive inhibition of bile acid synthesis by endogenous cholestanol and sitosterol in sitosterolemia with xanthomatosis. Effect on cholesterol 7 alpha-hydroxylase. J. Clin. Invest., 1988, 82(6), 1833-1839.
[http://dx.doi.org/10.1172/JCI113799] [PMID: 3143743]
[31]
Yu, L.; von Bergmann, K.; Lutjohann, D.; Hobbs, H.H.; Cohen, J.C. Selective sterol accumulation in ABCG5/ABCG8-deficient mice. J. Lipid Res., 2004, 45(2), 301-307.
[http://dx.doi.org/10.1194/jlr.M300377-JLR200] [PMID: 14657202]
[32]
Boergesen, M.; Pedersen, T.A.; Gross, B.; van Heeringen, S.J.; Hagenbeek, D.; Bindesbøll, C.; Caron, S.; Lalloyer, F.; Steffensen, K.R.; Nebb, H.I.; Gustafsson, J.A.; Stunnenberg, H.G.; Staels, B.; Mandrup, S. Genome-wide profiling of liver X receptor, retinoid X receptor, and peroxisome proliferator-activated receptor α in mouse liver reveals extensive sharing of binding sites. Mol. Cell. Biol., 2012, 32(4), 852-867.
[http://dx.doi.org/10.1128/MCB.06175-11] [PMID: 22158963]
[33]
Brown, D.A.; London, E. Functions of lipid rafts in biological membranes. Annu. Rev. Cell Dev. Biol., 1998, 14, 111-136.
[http://dx.doi.org/10.1146/annurev.cellbio.14.1.111] [PMID: 9891780]
[34]
Simons, K.; Ehehalt, R. Cholesterol, lipid rafts, and disease. J. Clin. Invest., 2002, 110(5), 597-603.
[http://dx.doi.org/10.1172/JCI0216390] [PMID: 12208858]
[35]
Simons, K.; Toomre, D. Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol., 2000, 1(1), 31-39.
[http://dx.doi.org/10.1038/35036052] [PMID: 11413487]
[36]
Lecerf, J.M.; de Lorgeril, M. Dietary cholesterol: from physiology to cardiovascular risk. Br. J. Nutr., 2011, 106(1), 6-14.
[http://dx.doi.org/10.1017/S0007114511000237] [PMID: 21385506]
[37]
Beck, J.G.; Mathieu, D.; Loudet, C.; Buchoux, S.; Dufourc, E.J. Plant sterols in “rafts”: a better way to regulate membrane thermal shocks. FASEB J., 2007, 21(8), 1714-1723.
[http://dx.doi.org/10.1096/fj.06-7809com] [PMID: 17317727]
[38]
Dufourc, E.J. The role of phytosterols in plant adaptation to temperature. Plant Signal. Behav., 2008, 3(2), 133-134.
[http://dx.doi.org/10.4161/psb.3.2.5051] [PMID: 19704733]
[39]
Vanmierlo, T.; Weingärtner, O.; van der Pol, S.; Husche, C.; Kerksiek, A.; Friedrichs, S.; Sijbrands, E.; Steinbusch, H.; Grimm, M.; Hartmann, T.; Laufs, U.; Böhm, M.; de Vries, H.E.; Mulder, M.; Lütjohann, D. Dietary intake of plant sterols stably increases plant sterol levels in the murine brain. J. Lipid Res., 2012, 53(4), 726-735.
[http://dx.doi.org/10.1194/jlr.M017244] [PMID: 22279184]
[40]
Hac-Wydro, K.; Wydro, P.; Dynarowicz-Łatka, P.; Paluch, M. Cholesterol and phytosterols effect on sphingomyelin/phosphatidylcholine model membranes--thermodynamic analysis of the interactions in ternary monolayers. J. Colloid Interface Sci., 2009, 329(2), 265-272.
[http://dx.doi.org/10.1016/j.jcis.2008.09.057] [PMID: 18922545]
[41]
Racette, S.B.; Lin, X.; Lefevre, M.; Spearie, C.A.; Most, M.M.; Ma, L.; Ostlund, R.E. Jr. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study. Am. J. Clin. Nutr., 2010, 91(1), 32-38.
[http://dx.doi.org/10.3945/ajcn.2009.28070] [PMID: 19889819]
[42]
Baker, W.L.; Baker, E.L.; Coleman, C.I. The effect of plant sterols or stanols on lipid parameters in patients with type 2 diabetes: a meta-analysis. Diabetes Res. Clin. Pract., 2009, 84(2), e33-e37.
[http://dx.doi.org/10.1016/j.diabres.2009.01.015] [PMID: 19243852]
[43]
Grundy, S.M.; Cleeman, J.I.; Merz, C.N.; Brewer, H.B., Jr; Clark, L.T.; Hunninghake, D.B.; Pasternak, R.C.; Smith, S.C. Jr.; Stone, N.J.; Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Arterioscler. Thromb. Vasc. Biol., 2004, 24(8), e149-e161.
[PMID: 15297292]
[44]
Maki, K.C.; Davidson, M.H.; Umporowicz, D.M.; Schaefer, E.J.; Dicklin, M.R.; Ingram, K.A.; Chen, S.; McNamara, J.R.; Gebhart, B.W.; Ribaya-Mercado, J.D.; Perrone, G.; Robins, S.J.; Franke, W.C. Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet. Am. J. Clin. Nutr., 2001, 74(1), 33-43.
[http://dx.doi.org/10.1093/ajcn/74.1.33] [PMID: 11451715]
[45]
Berge, K.E.; Tian, H.; Graf, G.A.; Yu, L.; Grishin, N.V.; Schultz, J.; Kwiterovich, P.; Shan, B.; Barnes, R.; Hobbs, H.H. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science, 2000, 290(5497), 1771-1775.
[http://dx.doi.org/10.1126/science.290.5497.1771] [PMID: 11099417]
[46]
Saher, G.; Stumpf, S.K. Cholesterol in myelin biogenesis and hypomyelinating disorders. Biochim. Biophys. Acta, 2015, 1851(8), 1083-1094.
[http://dx.doi.org/10.1016/j.bbalip.2015.02.010] [PMID: 25724171]
[47]
Dietschy, J.M. Central nervous system: cholesterol turnover, brain development and neurodegeneration. Biol. Chem., 2009, 390(4), 287-293.
[http://dx.doi.org/10.1515/BC.2009.035] [PMID: 19166320]
[48]
Morell, P.; Jurevics, H. Origin of cholesterol in myelin. Neurochem. Res., 1996, 21(4), 463-470.
[http://dx.doi.org/10.1007/BF02527711] [PMID: 8734440]
[49]
Chrast, R.; Saher, G.; Nave, K.A.; Verheijen, M.H. Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models. J. Lipid Res., 2011, 52(3), 419-434.
[http://dx.doi.org/10.1194/jlr.R009761] [PMID: 21062955]
[50]
Norton, W.T.; Poduslo, S.E. Myelination in rat brain: changes in myelin composition during brain maturation. J. Neurochem., 1973, 21(4), 759-773.
[http://dx.doi.org/10.1111/j.1471-4159.1973.tb07520.x] [PMID: 4754856]
[51]
Jansen, P.J.; Lütjohann, D.; Abildayeva, K.; Vanmierlo, T.; Plösch, T.; Plat, J.; von Bergmann, K.; Groen, A.K.; Ramaekers, F.C.; Kuipers, F.; Mulder, M. Dietary plant sterols accumulate in the brain. Biochim. Biophys. Acta, 2006, 1761(4), 445-453.
[http://dx.doi.org/10.1016/j.bbalip.2006.03.015] [PMID: 16677856]
[52]
Abbott, N.J.; Patabendige, A.A.; Dolman, D.E.; Yusof, S.R.; Begley, D.J. Structure and function of the blood-brain barrier. Neurobiol. Dis., 2010, 37(1), 13-25.
[http://dx.doi.org/10.1016/j.nbd.2009.07.030] [PMID: 19664713]
[53]
Stamatovic, S.M.; Keep, R.F.; Andjelkovic, A.V. Brain endothelial cell-cell junctions: how to “open” the blood brain barrier. Curr. Neuropharmacol., 2008, 6(3), 179-192.
[http://dx.doi.org/10.2174/157015908785777210] [PMID: 19506719]
[54]
Rubin, L.L.; Staddon, J.M. The cell biology of the blood-brain barrier. Annu. Rev. Neurosci., 1999, 22, 11-28.
[http://dx.doi.org/10.1146/annurev.neuro.22.1.11] [PMID: 10202530]
[55]
Saeed, A.A.; Genové, G.; Li, T.; Lütjohann, D.; Olin, M.; Mast, N.; Pikuleva, I.A.; Crick, P.; Wang, Y.; Griffiths, W.; Betsholtz, C.; Björkhem, I. Effects of a disrupted blood-brain barrier on cholesterol homeostasis in the brain. J. Biol. Chem., 2014, 289(34), 23712-23722.
[http://dx.doi.org/10.1074/jbc.M114.556159] [PMID: 24973215]
[56]
Smiljanic, K.; Vanmierlo, T.; Djordjevic, A.M.; Perovic, M.; Loncarevic-Vasiljkovic, N.; Tesic, V.; Rakic, L.; Ruzdijic, S.; Lutjohann, D.; Kanazir, S. Aging induces tissue-specific changes in cholesterol metabolism in rat brain and liver. Lipids, 2013, 48(11), 1069-1077.
[http://dx.doi.org/10.1007/s11745-013-3836-9] [PMID: 24057446]
[57]
Panzenboeck, U.; Balazs, Z.; Sovic, A.; Hrzenjak, A.; Levak-Frank, S.; Wintersperger, A.; Malle, E.; Sattler, W. ABCA1 and scavenger receptor class B, type I, are modulators of reverse sterol transport at an in vitro blood-brain barrier constituted of porcine brain capillary endothelial cells. J. Biol. Chem., 2002, 277(45), 42781-42789.
[http://dx.doi.org/10.1074/jbc.M207601200] [PMID: 12202492]
[58]
Lund, E.G.; Xie, C.; Kotti, T.; Turley, S.D.; Dietschy, J.M.; Russell, D.W. Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover. J. Biol. Chem., 2003, 278(25), 22980-22988.
[http://dx.doi.org/10.1074/jbc.M303415200] [PMID: 12686551]
[59]
Schoknecht, K.; Shalev, H. Blood-brain barrier dysfunction in brain diseases: clinical experience. Epilepsia, 2012, 53(Suppl. 6), 7-13.
[http://dx.doi.org/10.1111/j.1528-1167.2012.03697.x] [PMID: 23134490]
[60]
Ascherio, A.; Munger, K.L. Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann. Neurol., 2007, 61(4), 288-299.
[http://dx.doi.org/10.1002/ana.21117] [PMID: 17444504]
[61]
Ascherio, A.; Munger, K.L. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann. Neurol., 2007, 61(6), 504-513.
[http://dx.doi.org/10.1002/ana.21141] [PMID: 17492755]
[62]
Pugliatti, M.; Harbo, H.F.; Holmøy, T.; Kampman, M.T.; Myhr, K.M.; Riise, T.; Wolfson, C. Environmental risk factors in multiple sclerosis. Acta Neurol. Scand. Suppl., 2008, 188, 34-40.
[http://dx.doi.org/10.1111/j.1600-0404.2008.01029.x] [PMID: 18439219]
[63]
Soldan, S.S.; Jacobson, S. Role of viruses in etiology and pathogenesis of multiple sclerosis. Adv. Virus Res., 2001, 56, 517-555.
[http://dx.doi.org/10.1016/S0065-3527(01)56037-6] [PMID: 11450311]
[64]
Pugliatti, M.; Sotgiu, S.; Rosati, G. The worldwide prevalence of multiple sclerosis. Clin. Neurol. Neurosurg., 2002, 104(3), 182-191.
[http://dx.doi.org/10.1016/S0303-8467(02)00036-7] [PMID: 12127652]
[65]
Trapp, B.D.; Nave, K.A. Multiple sclerosis: an immune or neurodegenerative disorder? Annu. Rev. Neurosci., 2008, 31, 247-269.
[http://dx.doi.org/10.1146/annurev.neuro.30.051606.094313] [PMID: 18558855]
[66]
Nelissen, K.; Mulder, M.; Smets, I.; Timmermans, S.; Smeets, K.; Ameloot, M.; Hendriks, J.J. Liver X receptors regulate cholesterol homeostasis in oligodendrocytes. J. Neurosci. Res., 2012, 90(1), 60-71.
[http://dx.doi.org/10.1002/jnr.22743] [PMID: 21972082]
[67]
Jorissen, W.; Wouters, E.; Bogie, J.F.; Vanmierlo, T.; Noben, J.P.; Sviridov, D.; Hellings, N.; Somers, V.; Valcke, R.; Vanwijmeersch, B.; Stinissen, P.; Mulder, M.T.; Remaley, A.T.; Hendriks, J.J. Relapsing-remitting multiple sclerosis patients display an altered lipoprotein profile with dysfunctional HDL. Sci. Rep., 2017, 7, 43410.
[http://dx.doi.org/10.1038/srep43410] [PMID: 28230201]
[68]
Saher, G.; Brügger, B.; Lappe-Siefke, C.; Möbius, W.; Tozawa, R.; Wehr, M.C.; Wieland, F.; Ishibashi, S.; Nave, K.A. High cholesterol level is essential for myelin membrane growth. Nat. Neurosci., 2005, 8(4), 468-475.
[http://dx.doi.org/10.1038/nn1426] [PMID: 15793579]
[69]
Camargo, N.; Goudriaan, A.; van Deijk, A.F.; Otte, W.M.; Brouwers, J.F.; Lodder, H.; Gutmann, D.H.; Nave, K.A.; Dijkhuizen, R.M.; Mansvelder, H.D.; Chrast, R.; Smit, A.B.; Verheijen, M.H.G. Oligodendroglial myelination requires astrocyte-derived lipids. PLoS Biol., 2017, 15(5)e1002605
[http://dx.doi.org/10.1371/journal.pbio.1002605] [PMID: 28549068]
[70]
Berghoff, S.A.; Gerndt, N.; Winchenbach, J.; Stumpf, S.K.; Hosang, L.; Odoardi, F.; Ruhwedel, T.; Böhler, C.; Barrette, B.; Stassart, R.; Liebetanz, D.; Dibaj, P.; Möbius, W.; Edgar, J.M.; Saher, G. Dietary cholesterol promotes repair of demyelinated lesions in the adult brain. Nat. Commun., 2017, 8, 14241.
[http://dx.doi.org/10.1038/ncomms14241] [PMID: 28117328]
[71]
Miron, V.E.; Zehntner, S.P.; Kuhlmann, T.; Ludwin, S.K.; Owens, T.; Kennedy, T.E.; Bedell, B.J.; Antel, J.P. Statin therapy inhibits remyelination in the central nervous system. Am. J. Pathol., 2009, 174(5), 1880-1890.
[http://dx.doi.org/10.2353/ajpath.2009.080947] [PMID: 19349355]
[72]
Youssef, S.; Stüve, O.; Patarroyo, J.C.; Ruiz, P.J.; Radosevich, J.L.; Hur, E.M.; Bravo, M.; Mitchell, D.J.; Sobel, R.A.; Steinman, L.; Zamvil, S.S. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature, 2002, 420(6911), 78-84.
[http://dx.doi.org/10.1038/nature01158] [PMID: 12422218]
[73]
Stanislaus, R.; Singh, A.K.; Singh, I. Lovastatin treatment decreases mononuclear cell infiltration into the CNS of Lewis rats with experimental allergic encephalomyelitis. J. Neurosci. Res., 2001, 66(2), 155-162.
[http://dx.doi.org/10.1002/jnr.1207] [PMID: 11592110]
[74]
Pihl-Jensen, G.; Tsakiri, A.; Frederiksen, J.L. Statin treatment in multiple sclerosis: a systematic review and meta-analysis. CNS Drugs, 2015, 29(4), 277-291.
[http://dx.doi.org/10.1007/s40263-015-0239-x] [PMID: 25795002]
[75]
Desai, F.; Ramanathan, M.; Fink, C.S.; Wilding, G.E.; Weinstock-Guttman, B.; Awad, A.B. Comparison of the immunomodulatory effects of the plant sterol beta-sitosterol to simvastatin in peripheral blood cells from multiple sclerosis patients. Int. Immunopharmacol., 2009, 9(1), 153-157.
[http://dx.doi.org/10.1016/j.intimp.2008.10.019] [PMID: 19022404]
[76]
Choi, J.N.; Choi, Y.H.; Lee, J.M.; Noh, I.C.; Park, J.W.; Choi, W.S.; Choi, J.H. Anti-inflammatory effects of β-sitosterol-β-D-glucoside from Trachelospermum jasminoides (Apocynaceae) in lipopolysaccharide-stimulated RAW 264.7 murine macrophages. Nat. Prod. Res., 2012, 26(24), 2340-2343.
[http://dx.doi.org/10.1080/14786419.2012.654608] [PMID: 22292934]
[77]
Valerio, M.; Awad, A.B. β-Sitosterol down-regulates some pro-inflammatory signal transduction pathways by increasing the activity of tyrosine phosphatase SHP-1 in J774A.1 murine macrophages. Int. Immunopharmacol., 2011, 11(8), 1012-1017.
[http://dx.doi.org/10.1016/j.intimp.2011.02.018] [PMID: 21356343]
[78]
Valerio, M.S.; Minderman, H.; Mace, T.; Awad, A.B. β-Sitosterol modulates TLR4 receptor expression and intracellular MyD88-dependent pathway activation in J774A.1 murine macrophages. Cell. Immunol., 2013, 285(1-2), 76-83.
[http://dx.doi.org/10.1016/j.cellimm.2013.08.007] [PMID: 24121260]
[79]
Yoo, M.S.; Shin, J.S.; Choi, H.E.; Cho, Y.W.; Bang, M.H.; Baek, N.I.; Lee, K.T. Fucosterol isolated from Undaria pinnatifida inhibits lipopolysaccharide-induced production of nitric oxide and pro-inflammatory cytokines via the inactivation of nuclear factor-κB and p38 mitogen-activated protein kinase in RAW264.7 macrophages. Food Chem., 2012, 135(3), 967-975.
[http://dx.doi.org/10.1016/j.foodchem.2012.05.039] [PMID: 22953812]
[80]
Valerio, M.; Liu, H.B.; Heffner, R.; Zivadinov, R.; Ramanathan, M.; Weinstock-Guttman, B.; Awad, A.B. Phytosterols ameliorate clinical manifestations and inflammation in experimental autoimmune encephalomyelitis. Inflamm. Res., 2011, 60(5), 457-465.
[http://dx.doi.org/10.1007/s00011-010-0288-z] [PMID: 21136279]
[81]
Fricke, C.B.; Schrøder, M.; Poulsen, M.; von Bergmann, K.; Wester, I.; Knudsen, I.; Mortensen, A.; Lütjohann, D. Increased plant sterol and stanol levels in brain of Watanabe rabbits fed rapeseed oil derived plant sterol or stanol esters. Br. J. Nutr., 2007, 98(5), 890-899.
[http://dx.doi.org/10.1017/S0007114507756532] [PMID: 17537294]
[82]
Shi, C.; Wu, F.; Zhu, X.C.; Xu, J. Incorporation of beta-sitosterol into the membrane increases resistance to oxidative stress and lipid peroxidation via estrogen receptor-mediated PI3K/GSK3beta signaling. Biochim. Biophys. Acta, 2013, 1830(3), 2538-2544.
[http://dx.doi.org/10.1016/j.bbagen.2012.12.012] [PMID: 23266618]
[83]
Ohl, K.; Tenbrock, K.; Kipp, M. Oxidative stress in multiple sclerosis: Central and peripheral mode of action. Exp. Neurol., 2016, 277, 58-67.
[http://dx.doi.org/10.1016/j.expneurol.2015.11.010] [PMID: 26626971]
[84]
Zhao, C.; Dahlman-Wright, K. Liver X receptor in cholesterol metabolism. J. Endocrinol., 2010, 204(3), 233-240.
[http://dx.doi.org/10.1677/JOE-09-0271] [PMID: 19837721]
[85]
Plat, J.; Nichols, J.A.; Mensink, R.P. Plant sterols and stanols: effects on mixed micellar composition and LXR (target gene) activation. J. Lipid Res., 2005, 46(11), 2468-2476.
[http://dx.doi.org/10.1194/jlr.M500272-JLR200] [PMID: 16150823]
[86]
Janowski, B.A.; Willy, P.J.; Devi, T.R.; Falck, J.R.; Mangelsdorf, D.J. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature, 1996, 383(6602), 728-731.
[http://dx.doi.org/10.1038/383728a0] [PMID: 8878485]
[87]
Janowski, B.A.; Grogan, M.J.; Jones, S.A.; Wisely, G.B.; Kliewer, S.A.; Corey, E.J.; Mangelsdorf, D.J. Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc. Natl. Acad. Sci. USA, 1999, 96(1), 266-271.
[http://dx.doi.org/10.1073/pnas.96.1.266] [PMID: 9874807]
[88]
Wójcicka, G.; Jamroz-Wiśniewska, A.; Horoszewicz, K.; Bełtowski, J. Liver X receptors (LXRs). Part I: structure, function, regulation of activity, and role in lipid metabolism. Postepy Hig. Med. Dosw., 2007, 61, 736-759.
[PMID: 18063918]
[89]
Whitney, K.D.; Watson, M.A.; Collins, J.L.; Benson, W.G.; Stone, T.M.; Numerick, M.J.; Tippin, T.K.; Wilson, J.G.; Winegar, D.A.; Kliewer, S.A. Regulation of cholesterol homeostasis by the liver X receptors in the central nervous system. Mol. Endocrinol., 2002, 16(6), 1378-1385.
[http://dx.doi.org/10.1210/mend.16.6.0835] [PMID: 12040022]
[90]
Zelcer, N.; Tontonoz, P. Liver X receptors as integrators of metabolic and inflammatory signaling. J. Clin. Invest., 2006, 116(3), 607-614.
[http://dx.doi.org/10.1172/JCI27883] [PMID: 16511593]
[91]
Pascual-García, M.; Valledor, A.F. Biological roles of liver X receptors in immune cells. Arch. Immunol. Ther. Exp. (Warsz.), 2012, 60(4), 235-249.
[http://dx.doi.org/10.1007/s00005-012-0179-9] [PMID: 22696047]
[92]
Treuter, E.; Venteclef, N. Transcriptional control of metabolic and inflammatory pathways by nuclear receptor SUMOylation. Biochim. Biophys. Acta, 2011, 1812(8), 909-918.
[http://dx.doi.org/10.1016/j.bbadis.2010.12.008] [PMID: 21172431]
[93]
Treuter, E. New wrestling rules of anti-inflammatory transrepression by oxysterol receptor LXR revealed. Cell Res., 2011, 21(5), 711-714.
[http://dx.doi.org/10.1038/cr.2011.52] [PMID: 21445093]
[94]
Bogie, J.F.; Timmermans, S.; Huynh-Thu, V.A.; Irrthum, A.; Smeets, H.J.; Gustafsson, J.A.; Steffensen, K.R.; Mulder, M.; Stinissen, P.; Hellings, N.; Hendriks, J.J. Myelin-derived lipids modulate macrophage activity by liver X receptor activation. PLoS One, 2012, 7(9)e44998
[http://dx.doi.org/10.1371/journal.pone.0044998] [PMID: 22984598]
[95]
Cui, G.; Qin, X.; Wu, L.; Zhang, Y.; Sheng, X.; Yu, Q.; Sheng, H.; Xi, B.; Zhang, J.Z.; Zang, Y.Q. Liver X receptor (LXR) mediates negative regulation of mouse and human Th17 differentiation. J. Clin. Invest., 2011, 121(2), 658-670.
[http://dx.doi.org/10.1172/JCI42974] [PMID: 21266776]
[96]
Tall, A.R.; Yvan-Charvet, L. Cholesterol, inflammation and innate immunity. Nat. Rev. Immunol., 2015, 15(2), 104-116.
[http://dx.doi.org/10.1038/nri3793] [PMID: 25614320]
[97]
Meffre, D.; Shackleford, G.; Hichor, M.; Gorgievski, V.; Tzavara, E.T.; Trousson, A.; Ghoumari, A.M.; Deboux, C.; Nait Oumesmar, B.; Liere, P.; Schumacher, M.; Baulieu, E.E.; Charbonnier, F.; Grenier, J.; Massaad, C. Liver X receptors alpha and beta promote myelination and remyelination in the cerebellum. Proc. Natl. Acad. Sci. USA, 2015, 112(24), 7587-7592.
[http://dx.doi.org/10.1073/pnas.1424951112] [PMID: 26023184]
[98]
Vivancos, M.; Moreno, J.J. beta-Sitosterol modulates antioxidant enzyme response in RAW 264.7 macrophages. Free Radic. Biol. Med., 2005, 39(1), 91-97.
[http://dx.doi.org/10.1016/j.freeradbiomed.2005.02.025] [PMID: 15925281]
[99]
Gutendorf, B.; Westendorf, J. Comparison of an array of in vitro assays for the assessment of the estrogenic potential of natural and synthetic estrogens, phytoestrogens and xenoestrogens. Toxicology, 2001, 166(1-2), 79-89.
[http://dx.doi.org/10.1016/S0300-483X(01)00437-1] [PMID: 11518614]
[100]
Plat, J.; Hendrikx, T.; Bieghs, V.; Jeurissen, M.L.; Walenbergh, S.M.; van Gorp, P.J.; De Smet, E.; Konings, M.; Vreugdenhil, A.C.; Guichot, Y.D.; Rensen, S.S.; Buurman, W.A.; Greve, J.W.; Lütjohann, D.; Mensink, R.P.; Shiri-Sverdlov, R. Protective role of plant sterol and stanol esters in liver inflammation: insights from mice and humans. PLoS One, 2014, 9(10)e110758
[http://dx.doi.org/10.1371/journal.pone.0110758] [PMID: 25356831]
[101]
McDaniel, A.L.; Alger, H.M.; Sawyer, J.K.; Kelley, K.L.; Kock, N.D.; Brown, J.M.; Temel, R.E.; Rudel, L.L. Phytosterol feeding causes toxicity in ABCG5/G8 knockout mice. Am. J. Pathol., 2013, 182(4), 1131-1138.
[http://dx.doi.org/10.1016/j.ajpath.2012.12.014] [PMID: 23380580]
[102]
Grefhorst, A.; Elzinga, B.M.; Voshol, P.J.; Plösch, T.; Kok, T.; Bloks, V.W.; van der Sluijs, F.H.; Havekes, L.M.; Romijn, J.A.; Verkade, H.J.; Kuipers, F. Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles. J. Biol. Chem., 2002, 277(37), 34182-34190.
[http://dx.doi.org/10.1074/jbc.M204887200] [PMID: 12097330]
[103]
Repa, J.J.; Berge, K.E.; Pomajzl, C.; Richardson, J.A.; Hobbs, H.; Mangelsdorf, D.J. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J. Biol. Chem., 2002, 277(21), 18793-18800.
[http://dx.doi.org/10.1074/jbc.M109927200] [PMID: 11901146]
[104]
Repa, J.J.; Liang, G.; Ou, J.; Bashmakov, Y.; Lobaccaro, J.M.; Shimomura, I.; Shan, B.; Brown, M.S.; Goldstein, J.L.; Mangelsdorf, D.J. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev., 2000, 14(22), 2819-2830.
[http://dx.doi.org/10.1101/gad.844900] [PMID: 11090130]
[105]
Schultz, J.R.; Tu, H.; Luk, A.; Repa, J.J.; Medina, J.C.; Li, L.; Schwendner, S.; Wang, S.; Thoolen, M.; Mangelsdorf, D.J.; Lustig, K.D.; Shan, B. Role of LXRs in control of lipogenesis. Genes Dev., 2000, 14(22), 2831-2838.
[http://dx.doi.org/10.1101/gad.850400] [PMID: 11090131]
[106]
Wilund, K.R.; Yu, L.; Xu, F.; Hobbs, H.H.; Cohen, J.C. High-level expression of ABCG5 and ABCG8 attenuates diet-induced hypercholesterolemia and atherosclerosis in Ldlr-/- mice. J. Lipid Res., 2004, 45(8), 1429-1436.
[http://dx.doi.org/10.1194/jlr.M400167-JLR200] [PMID: 15175362]
[107]
Alexander, J.S.; Zivadinov, R.; Maghzi, A.H.; Ganta, V.C.; Harris, M.K.; Minagar, A. Multiple sclerosis and cerebral endothelial dysfunction: Mechanisms. Pathophysiology, 2011, 18(1), 3-12.
[http://dx.doi.org/10.1016/j.pathophys.2010.04.002] [PMID: 20663648]
[108]
Lee, S.; Marharjan, S.; Jung, J.W.; Kim, N.J.; Kim, K.; Han, Y.T.; Lim, C.; Choi, H.J.; Kwon, Y.G.; Suh, Y.G. Novel human umbilical vein endothelial cells (HUVEC)-apoptosis inhibitory phytosterol analogues: insight into their structure-activity relationships. Arch. Pharm. Res., 2012, 35(3), 455-460.
[http://dx.doi.org/10.1007/s12272-012-0308-3] [PMID: 22477192]
[109]
Bustos, P.; Duffau, C.; Pacheco, C.; Ulloa, N. beta-Sitosterol modulation of monocyte-endothelial cell interaction: a comparison to female hormones. Maturitas, 2008, 60(3-4), 202-208.
[http://dx.doi.org/10.1016/j.maturitas.2008.06.002] [PMID: 18676106]
[110]
Loizou, S.; Lekakis, I.; Chrousos, G.P.; Moutsatsou, P. Beta-sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells. Mol. Nutr. Food Res., 2010, 54(4), 551-558.
[http://dx.doi.org/10.1002/mnfr.200900012] [PMID: 19937850]
[111]
Gupta, P.; Balwani, S.; Kumar, S.; Aggarwal, N.; Rossi, M.; Paumier, S.; Caruso, F.; Bovicelli, P.; Saso, L.; DePass, A.L.; Prasad, A.K.; Parmar, V.S.; Ghosh, B. beta-sitosterol among other secondary metabolites of Piper galeatum shows inhibition of TNFalpha-induced cell adhesion molecule expression on human endothelial cells. Biochimie, 2010, 92(9), 1213-1221.
[http://dx.doi.org/10.1016/j.biochi.2010.06.005] [PMID: 20558233]
[112]
Weingärtner, O.; Ulrich, C.; Lütjohann, D.; Ismail, K.; Schirmer, S.H.; Vanmierlo, T.; Böhm, M.; Laufs, U. Differential effects on inhibition of cholesterol absorption by plant stanol and plant sterol esters in apoE-/- mice. Cardiovasc. Res., 2011, 90(3), 484-492.
[http://dx.doi.org/10.1093/cvr/cvr020] [PMID: 21257611]
[113]
Nam, Y.; Lee, D. Ameliorating effects of constituents from Cortex Acanthopanacis Radicis on memory impairment in mice induced by scopolamine. J. Tradit. Chin. Med., 2014, 34(1), 57-62.
[http://dx.doi.org/10.1016/S0254-6272(14)60055-8] [PMID: 25102692]
[114]
Weingärtner, O.; Lütjohann, D.; Ji, S.; Weisshoff, N.; List, F.; Sudhop, T.; von Bergmann, K.; Gertz, K.; König, J.; Schäfers, H.J.; Endres, M.; Böhm, M.; Laufs, U. Vascular effects of diet supplementation with plant sterols. J. Am. Coll. Cardiol., 2008, 51(16), 1553-1561.
[http://dx.doi.org/10.1016/j.jacc.2007.09.074] [PMID: 18420097]
[115]
Yang, C.; Chen, Z.Y.; Wong, S.L.; Liu, J.; Liang, Y.T.; Lau, C.W.; Lee, H.K.; Huang, Y.; Tsang, S.Y. β-Sitosterol oxidation products attenuate vasorelaxation by increasing reactive oxygen species and cyclooxygenase-2. Cardiovasc. Res., 2013, 97(3), 520-532.
[http://dx.doi.org/10.1093/cvr/cvs370] [PMID: 23250922]
[116]
Parihar, M.S.; Hemnani, T. Alzheimer’s disease pathogenesis and therapeutic interventions. J. Clin. Neurosci., 2004, 11(5), 456-467.
[http://dx.doi.org/10.1016/j.jocn.2003.12.007] [PMID: 15177383]
[117]
Heppner, F.L.; Ransohoff, R.M.; Becher, B. Immune attack: the role of inflammation in Alzheimer disease. Nat. Rev. Neurosci., 2015, 16(6), 358-372.
[http://dx.doi.org/10.1038/nrn3880] [PMID: 25991443]
[118]
Goodenough, S.; Schäfer, M.; Behl, C. Estrogen-induced cell signalling in a cellular model of Alzheimer’s disease. J. Steroid Biochem. Mol. Biol., 2003, 84(2-3), 301-305.
[http://dx.doi.org/10.1016/S0960-0760(03)00043-8] [PMID: 12711016]
[119]
Sisodia, S.S.; St George-Hyslop, P.H. gamma-Secretase, Notch, Abeta and Alzheimer’s disease: where do the presenilins fit in? Nat. Rev. Neurosci., 2002, 3(4), 281-290.
[http://dx.doi.org/10.1038/nrn785] [PMID: 11967558]
[120]
Mulder, M. Sterols in the central nervous system. Curr. Opin. Clin. Nutr. Metab. Care, 2009, 12(2), 152-158.
[http://dx.doi.org/10.1097/MCO.0b013e32832182da] [PMID: 19202386]
[121]
Shobab, L.A.; Hsiung, G.Y.; Feldman, H.H. Cholesterol in Alzheimer’s disease. Lancet Neurol., 2005, 4(12), 841-852.
[http://dx.doi.org/10.1016/S1474-4422(05)70248-9] [PMID: 16297842]
[122]
Stefani, M.; Liguri, G. Cholesterol in Alzheimer’s disease: unresolved questions. Curr. Alzheimer Res., 2009, 6(1), 15-29.
[http://dx.doi.org/10.2174/156720509787313899] [PMID: 19199871]
[123]
Popp, J.; Lewczuk, P.; Kölsch, H.; Meichsner, S.; Maier, W.; Kornhuber, J.; Jessen, F.; Lütjohann, D. Cholesterol metabolism is associated with soluble amyloid precursor protein production in Alzheimer’s disease. J. Neurochem., 2012, 123(2), 310-316.
[http://dx.doi.org/10.1111/j.1471-4159.2012.07893.x] [PMID: 22845771]
[124]
Liu, C.C.; Liu, C.C.; Kanekiyo, T.; Xu, H.; Bu, G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat. Rev. Neurol., 2013, 9(2), 106-118.
[http://dx.doi.org/10.1038/nrneurol.2012.263] [PMID: 23296339]
[125]
Shafaati, M.; Marutle, A.; Pettersson, H.; Lövgren-Sandblom, A.; Olin, M.; Pikuleva, I.; Winblad, B.; Nordberg, A.; Björkhem, I. Marked accumulation of 27-hydroxycholesterol in the brains of Alzheimer’s patients with the Swedish APP 670/671 mutation. J. Lipid Res., 2011, 52(5), 1004-1010.
[http://dx.doi.org/10.1194/jlr.M014548] [PMID: 21335619]
[126]
Kölsch, H.; Heun, R.; Jessen, F.; Popp, J.; Hentschel, F.; Maier, W.; Lütjohann, D. Alterations of cholesterol precursor levels in Alzheimer’s disease. Biochim. Biophys. Acta, 2010, 1801(8), 945-950.
[http://dx.doi.org/10.1016/j.bbalip.2010.03.001] [PMID: 20226877]
[127]
Kölsch, H.; Heun, R.; Kerksiek, A.; Bergmann, K.V.; Maier, W.; Lütjohann, D. Altered levels of plasma 24S- and 27-hydroxycholesterol in demented patients. Neurosci. Lett., 2004, 368(3), 303-308.
[http://dx.doi.org/10.1016/j.neulet.2004.07.031] [PMID: 15364416]
[128]
Vanmierlo, T.; Bloks, V.W.; van Vark-van der Zee, L.C.; Rutten, K.; Kerksiek, A.; Friedrichs, S.; Sijbrands, E.; Steinbusch, H.W.; Kuipers, F.; Lütjohann, D.; Mulder, M. Alterations in brain cholesterol metabolism in the APPSLxPS1mut mouse, a model for Alzheimer’s disease. J. Alzheimers Dis., 2010, 19(1), 117-127.
[http://dx.doi.org/10.3233/JAD-2010-1209] [PMID: 20061631]
[129]
Fassbender, K.; Simons, M.; Bergmann, C.; Stroick, M.; Lutjohann, D.; Keller, P.; Runz, H.; Kuhl, S.; Bertsch, T.; von Bergmann, K.; Hennerici, M.; Beyreuther, K.; Hartmann, T. Simvastatin strongly reduces levels of Alzheimer’s disease beta -amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc. Natl. Acad. Sci. USA, 2001, 98(10), 5856-5861.
[http://dx.doi.org/10.1073/pnas.081620098] [PMID: 11296263]
[130]
Grimm, M.O.; Zimmer, V.C.; Lehmann, J.; Grimm, H.S.; Hartmann, T. The impact of cholesterol, DHA, and sphingolipids on Alzheimer’s disease. BioMed Res. Int., 2013, 2013814390
[http://dx.doi.org/10.1155/2013/814390] [PMID: 24575399]
[131]
Marquer, C.; Devauges, V.; Cossec, J.C.; Liot, G.; Lécart, S.; Saudou, F.; Duyckaerts, C.; Lévêque-Fort, S.; Potier, M.C. Local cholesterol increase triggers amyloid precursor protein-Bace1 clustering in lipid rafts and rapid endocytosis. FASEB J., 2011, 25(4), 1295-1305.
[http://dx.doi.org/10.1096/fj.10-168633] [PMID: 21257714]
[132]
Burg, V.K.; Grimm, H.S.; Rothhaar, T.L.; Grösgen, S.; Hundsdörfer, B.; Haupenthal, V.J.; Zimmer, V.C.; Mett, J.; Weingärtner, O.; Laufs, U.; Broersen, L.M.; Tanila, H.; Vanmierlo, T.; Lütjohann, D.; Hartmann, T.; Grimm, M.O. Plant sterols the better cholesterol in Alzheimer’s disease? A mechanistical study. J. Neurosci., 2013, 33(41), 16072-16087.
[http://dx.doi.org/10.1523/JNEUROSCI.1506-13.2013] [PMID: 24107941]
[133]
Koivisto, H.; Grimm, M.O.; Rothhaar, T.L.; Berkecz, R.; Lütjohann D, D.; Giniatullina, R.; Takalo, M.; Miettinen, P.O.; Lahtinen, H.M.; Giniatullin, R.; Penke, B.; Janáky, T.; Broersen, L.M.; Hartmann, T.; Tanila, H. Special lipid-based diets alleviate cognitive deficits in the APPswe/PS1dE9 transgenic mouse model of Alzheimer’s disease independent of brain amyloid deposition. J. Nutr. Biochem., 2014, 25(2), 157-169.
[http://dx.doi.org/10.1016/j.jnutbio.2013.09.015] [PMID: 24445040]
[134]
Shi, C.; Liu, J.; Wu, F.; Zhu, X.; Yew, D.T.; Xu, J. β-sitosterol inhibits high cholesterol-induced platelet β-amyloid release. J. Bioenerg. Biomembr., 2011, 43(6), 691-697.
[http://dx.doi.org/10.1007/s10863-011-9383-2] [PMID: 21969169]
[135]
Jiang, Q.; Lee, C.Y.; Mandrekar, S.; Wilkinson, B.; Cramer, P.; Zelcer, N.; Mann, K.; Lamb, B.; Willson, T.M.; Collins, J.L.; Richardson, J.C.; Smith, J.D.; Comery, T.A.; Riddell, D.; Holtzman, D.M.; Tontonoz, P.; Landreth, G.E. ApoE promotes the proteolytic degradation of Abeta. Neuron, 2008, 58(5), 681-693.
[http://dx.doi.org/10.1016/j.neuron.2008.04.010] [PMID: 18549781]
[136]
Terwel, D.; Steffensen, K.R.; Verghese, P.B.; Kummer, M.P.; Gustafsson, J.A.; Holtzman, D.M.; Heneka, M.T. Critical role of astroglial apolipoprotein E and liver X receptor-α expression for microglial Aβ phagocytosis. J. Neurosci., 2011, 31(19), 7049-7059.
[http://dx.doi.org/10.1523/JNEUROSCI.6546-10.2011] [PMID: 21562267]
[137]
Ghisletti, S.; Huang, W.; Ogawa, S.; Pascual, G.; Lin, M.E.; Willson, T.M.; Rosenfeld, M.G.; Glass, C.K. Parallel SUMOylation-dependent pathways mediate gene- and signal-specific transrepression by LXRs and PPARgamma. Mol. Cell, 2007, 25(1), 57-70.
[http://dx.doi.org/10.1016/j.molcel.2006.11.022] [PMID: 17218271]
[138]
Prokop, S.; Miller, K.R.; Heppner, F.L. Microglia actions in Alzheimer’s disease. Acta Neuropathol., 2013, 126(4), 461-477.
[http://dx.doi.org/10.1007/s00401-013-1182-x] [PMID: 24224195]
[139]
Gandy, S.; Heppner, F.L. Microglia as dynamic and essential components of the amyloid hypothesis. Neuron, 2013, 78(4), 575-577.
[http://dx.doi.org/10.1016/j.neuron.2013.05.007] [PMID: 23719156]
[140]
Perry, V.H.; Holmes, C. Microglial priming in neurodegenerative disease. Nat. Rev. Neurol., 2014, 10(4), 217-224.
[http://dx.doi.org/10.1038/nrneurol.2014.38] [PMID: 24638131]
[141]
Cunningham, C. Microglia and neurodegeneration: the role of systemic inflammation. Glia, 2013, 61(1), 71-90.
[http://dx.doi.org/10.1002/glia.22350] [PMID: 22674585]
[142]
Sudduth, T.L.; Schmitt, F.A.; Nelson, P.T.; Wilcock, D.M. Neuroinflammatory phenotype in early Alzheimer’s disease. Neurobiol. Aging, 2013, 34(4), 1051-1059.
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.09.012] [PMID: 23062700]
[143]
Krstic, D.; Knuesel, I. Deciphering the mechanism underlying late-onset Alzheimer disease. Nat. Rev. Neurol., 2013, 9(1), 25-34.
[http://dx.doi.org/10.1038/nrneurol.2012.236] [PMID: 23183882]
[144]
Xu, X.; Bittman, R.; Duportail, G.; Heissler, D.; Vilcheze, C.; London, E. Effect of the structure of natural sterols and sphingolipids on the formation of ordered sphingolipid/sterol domains (rafts). Comparison of cholesterol to plant, fungal, and disease-associated sterols and comparison of sphingomyelin, cerebrosides, and ceramide. J. Biol. Chem., 2001, 276(36), 33540-33546.
[http://dx.doi.org/10.1074/jbc.M104776200] [PMID: 11432870]
[145]
Wang, J.; Wu, F.; Shi, C. Substitution of membrane cholesterol with β-sitosterol promotes nonamyloidogenic cleavage of endogenous amyloid precursor protein. Neuroscience, 2013, 247, 227-233.
[http://dx.doi.org/10.1016/j.neuroscience.2013.05.022] [PMID: 23707801]
[146]
Vanmierlo, T.; Popp, J.; Kölsch, H.; Friedrichs, S.; Jessen, F.; Stoffel-Wagner, B.; Bertsch, T.; Hartmann, T.; Maier, W.; von Bergmann, K.; Steinbusch, H.; Mulder, M.; Lütjohann, D. The plant sterol brassicasterol as additional CSF biomarker in Alzheimer’s disease. Acta Psychiatr. Scand., 2011, 124(3), 184-192.
[http://dx.doi.org/10.1111/j.1600-0447.2011.01713.x] [PMID: 21585343]
[147]
Serot, J.M.; Béné, M.C.; Foliguet, B.; Faure, G.C. Morphological alterations of the choroid plexus in late-onset Alzheimer’s disease. Acta Neuropathol., 2000, 99(2), 105-108.
[http://dx.doi.org/10.1007/PL00007412] [PMID: 10672315]
[148]
Baskar, A.A.; Ignacimuthu, S.; Paulraj, G.M.; Al Numair, K.S. Chemopreventive potential of beta-Sitosterol in experimental colon cancer model--an in vitro and In vivo study. BMC Complement. Altern. Med., 2010, 10, 24.
[http://dx.doi.org/10.1186/1472-6882-10-24] [PMID: 20525330]
[149]
Woyengo, T.A.; Ramprasath, V.R.; Jones, P.J. Anticancer effects of phytosterols. Eur. J. Clin. Nutr., 2009, 63(7), 813-820.
[http://dx.doi.org/10.1038/ejcn.2009.29] [PMID: 19491917]


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VOLUME: 26
ISSUE: 37
Year: 2019
Page: [6750 - 6765]
Pages: 16
DOI: 10.2174/0929867325666180706113844
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