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Liver X receptors in the central nervous system: From lipid homeostasis to neuronal degeneration
Open accessAbstract
Liver X receptors (LXRα and -β) are nuclear receptors abundant in the liver where they are regulators of lipid homeostasis. Both LXRs are also expressed in the brain, but their roles in this tissue remain to be clarified. We examined the brains of mice in which the genes of both LXRα and -β have been disrupted and found several severe abnormalities. One of the most striking features is that the lateral ventricles are closed and lined with lipid-laden cells. In addition, there are enlarged brain blood vessels, especially in the pars reticularis of the substantia nigra and in the globus pallidus. Other features of the brains are excessive lipid deposits, proliferation of astrocytes, loss of neurons, and disorganized myelin sheaths. Electron micrographs revealed that, as mice aged, lipid vacuoles accumulated in astrocytes surrounding blood vessels. Comparison of mRNA profiles in LXR knockout mice and wild-type littermates showed that expression of several LXR target genes involved in cholesterol efflux from astrocytes was reduced. These findings show that LXRs have an important function in lipid homeostasis in the brain, and that loss of these receptors results in neurodegenerative diseases. Further characterization of the role of LXRs in the brain could lead to new insights into the etiology and treatment of some neurodegenerative disorders.
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Cites
CNS synaptogenesis promoted by glia-derived cholesterol
Mauch, D. H., Nägler, K., Schumacher, S., Göritz, C., Müller, E.-C., Otto, A., & Pfrieger, F. W. (2001) · Science · doi:10.1126/science.294.5545.1354 · Cited by 1,711
Activation of the Nuclear Receptor LXR by Oxysterols Defines a New Hormone Response Pathway
Lehmann, J. M., Kliewer, S. A., Moore, L. B., Smith-Oliver, T. A., Oliver, B. B., Su, J.-L., Sundseth, S. S., Winegar, D. A., Blanchard, D. E., Spencer, T. A., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.6.3137 · Cited by 1,233
Cerebral microvascular pathology in aging and Alzheimer's disease
Farkas, E., & Luiten, P. G. M. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00068-x · Cited by 1,102
Cholesterol metabolism in the brain
Dietschy, J. M., & Turley, S. D. (2001) · Current Opinion in Lipidology · doi:10.1097/00041433-200104000-00003 · Cited by 906
Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins
Pitas, R. E., Boyles, J. K., Lee, S. H., Foss, D., & Mahley, R. W. (1987) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(87)90295-5 · Cited by 693
Dehouck, B., Dehouck, M. P., Fruchart, J. C., & Cecchelli, R. (1994) · The Journal of cell biology · doi:10.1083/jcb.126.2.465 · Cited by 240
Cited by
Dietschy, J. M., & Turley, S. D. (2004) · Journal of Lipid Research · doi:10.1194/jlr.r400004-jlr200 · Cited by 1,095
Brain Cholesterol: Long Secret Life Behind a Barrier
Björkhem, I., & Meaney, S. (2004) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000120374.59826.1b · Cited by 1,044
Glial Lipid Droplets and ROS Induced by Mitochondrial Defects Promote Neurodegeneration
Liu, L., Zhang, K., Sandoval, H., Yamamoto, S., Jaiswal, M., Sanz, E., Li, Z., Hui, J., Graham, B. H., Quintana, A., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.019 · Cited by 876
ApoE Promotes the Proteolytic Degradation of Aβ
Jiang, Q., Lee, C. Y. D., Mandrekar, S., Wilkinson, B., Cramer, P., Zelcer, N., Mann, K., Lamb, B., Willson, T. M., Collins, J. L., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.04.010 · Cited by 876
Liver X receptors in lipid signalling and membrane homeostasis
Wang, B., & Tontonoz, P. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0037-x · Cited by 722
Liver X receptors in lipid metabolism: opportunities for drug discovery
Hong, C., & Tontonoz, P. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4280 · Cited by 587
Casserly, I., & Topol, E. J. (2004) · The Lancet · doi:10.1016/s0140-6736(04)15900-x · Cited by 560
Cholesterol homeostasis and function in neurons of the central nervous system
Pfrieger, F. W. (2003) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3018-7 · Cited by 453
Central nervous system: cholesterol turnover, brain development and neurodegeneration
Dietschy, J. M. (2009) · bchm · doi:10.1515/bc.2009.035 · Cited by 394
Martins, I. J., Hone, E., Foster, J. K., Sünram-Lea, S. I., Gnjec, A., Fuller, S. J., Nolan, D., Gandy, S. E., & Martins, R. N. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001854 · Cited by 388
Attenuation of neuroinflammation and Alzheimer's disease pathology by liver x receptors
Zelcer, N., Khanlou, N., Clare, R., Jiang, Q., Reed-Geaghan, E. G., Landreth, G. E., Vinters, H. V., & Tontonoz, P. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701096104 · Cited by 358
Cholesterol: its regulation and role in central nervous system disorders
Orth, M., & Bellosta, S. (2012) · Cholesterol · doi:10.1155/2012/292598 · Cited by 339
Cholesterol in brain disease: Sometimes determinant and frequently implicated
Martín, M. G., Pfrieger, F., & Dotti, C. G. (2014) · The EMBO Reports · doi:10.15252/embr.201439225 · Cited by 304
Koldamova, R. P., Lefterov, I. M., Staufenbiel, M., Wolfe, D., Huang, S., Glorioso, J. C., Walter, M., Roth, M. G., & Lazo, J. S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411420200 · Cited by 279
Fernandez, C. G., Hamby, M. E., McReynolds, M. L., & Ray, W. J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00014 · Cited by 277
Abildayeva, K., Jansen, P. J., Hirsch-Reinshagen, V., Bloks, V. W., Bakker, A. H. F., Ramaekers, F. C. S., de Vente, J., Groen, A. K., Wellington, Kuipers, F., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601019200 · Cited by 267
Riddell, D. R., Zhou, H., Comery, T. A., Kouranova, E., Lo, C. F., Warwick, H. K., Ring, R. H., Kirksey, Y., Aschmies, S., Xu, J., et al. (2007) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2007.01.011 · Cited by 244
Koldamova, R. P., Lefterov, I. M., Ikonomovic, M. D., Skoko, J., Lefterov, P. I., Isanski, B. A., DeKosky, S. T., & Lazo, J. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300044200 · Cited by 237
Kim, W. S., Rahmanto, A. S., Kamili, A., Rye, K.-A., Guillemin, G. J., Gelissen, I. C., Jessup, W., Hill, A. F., & Garner, B. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607831200 · Cited by 191
LXR Regulation of Brain Cholesterol: From Development to Disease
Courtney, R., & Landreth, G. E. (2016) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2016.03.018 · Cited by 190
Terwel, D., Steffensen, K. R., Verghese, P. B., Kummer, M. P., Gustafsson, J.-Å., Holtzman, D. M., & Heneka, M. T. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.6546-10.2011 · Cited by 190
Self-citationOxidized cholesterol as the driving force behind the development of Alzheimer’s disease
Gamba, P., Testa, G., Gargiulo, S., Staurenghi, E., Poli, G., & Leonarduzzi, G. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00119 · Cited by 180
Expression of Liver X Receptor Target Genes Decreases Cellular Amyloid β Peptide Secretion
Sun, Y., Yao, J., Kim, T.-W., & Tall, A. R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300760200 · Cited by 179
Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse
Quan, G., Xie, C., Dietschy, J. M., & Turley, S. D. (2003) · Developmental Brain Research · doi:10.1016/j.devbrainres.2003.09.015 · Cited by 177
Liang, Y., Lin, S., Beyer, T. P., Zhang, Y., Wu, X., Bales, K. R., DeMattos, R. B., May, P. C., Li, S. D., Jiang, X., et al. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02183.x · Cited by 160
Formation and function of apolipoprotein E-containing lipoproteins in the nervous system
Vance, J. E., & Hayashi, H. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.02.007 · Cited by 155
Lipid Transport and Metabolism at the Blood-Brain Interface: Implications in Health and Disease
Pifferi, F., Laurent, B., & Plourde, M. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.645646 · Cited by 148
ATP-binding cassette transporter A1: From metabolism to neurodegeneration
Koldamova, R., Fitz, N. F., & Lefterov, I. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.007 · Cited by 144
Lipids in the nervous system: From biochemistry and molecular biology to patho-physiology
Cermenati, G., Mitro, N., Audano, M., Melcangi, R. C., Crestani, M., De Fabiani, E., & Caruso, D. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.08.011 · Cited by 137
Kim, H.-J., Fan, X., Gabbi, C., Yakimchuk, K., Parini, P., Warner, M., & Gustafsson, J.-Å. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711599105 · Cited by 136
Self-citationNuclear receptors as therapeutic targets for Alzheimer's disease
Mandrekar-Colucci, S., & Landreth, G. E. (2011) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.594043 · Cited by 126
Structure of the retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on DNA
Lou, X., Toresson, G., Benod, C., Suh, J. H., Philips, K. J., Webb, P., & Gustafsson, J.-A. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2778 · Cited by 105
Self-citationFan, X., Kim, H.-J., Bouton, D., Warner, M., & Gustafsson, J.-Å. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806974105 · Cited by 103
Self-citationNuclear receptors in neurodegenerative diseases
Skerrett, R., Malm, T., & Landreth, G. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.019 · Cited by 94
Lipid metabolism and neuroinflammation in Alzheimer’s disease: a role for liver X receptors
Kang, J., & Rivest, S. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1049 · Cited by 94
Han, X., Zhu, J., Zhang, X., Song, Q., Ding, J., Lu, M., Sun, S., & Hu, G. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00397 · Cited by 91
Liver X receptors regulate cholesterol homeostasis in oligodendrocytes
Nelissen, K., Mulder, M., Smets, I., Timmermans, S., Smeets, K., Ameloot, M., & Hendriks, J. J. A. (2012) · Journal of Neuroscience Research · doi:10.1002/jnr.22743 · Cited by 80
Brain cholesterol metabolism and neurologic disease
Benarroch, E. E. (2008) · Neurology · doi:10.1212/01.wnl.0000333215.93440.36 · Cited by 68
Liver X receptors: Emerging therapeutic targets for Alzheimer's disease
Sodhi, R. K., & Singh, N. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2013.03.008 · Cited by 61
Fujiyoshi, M., Ohtsuki, S., Hori, S., Tachikawa, M., & Terasaki, T. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04240.x · Cited by 56
Sorrentino, V., & Zelcer, N. (2012) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3283532947 · Cited by 55
Milagre, I., Nunes, M. J., Gama, M. J., Silva, R. F., Pascussi, J. M., Lechner, M. C., & Rodrigues, E. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05442.x · Cited by 40
Brain cholesterol homeostasis and its association with neurodegenerative diseases
Gao, Y., Ye, S., Tang, Y., Tong, W., & Sun, S. (2023) · Neurochemistry International · doi:10.1016/j.neuint.2023.105635 · Cited by 38
Balancing cholesterol in the brain: from synthesis to disposal
Qian, L., Chai, A. B., Gelissen, I. C., & Brown, A. J. (2022) · Exploration of Neuroprotective Therapy · doi:10.37349/ent.2022.00015 · Cited by 31
Liver X receptors regulate cerebrospinal fluid production
Dai, Y.-B., Wu, W.-F., Huang, B., Miao, Y.-F., Nadarshina, S., Warner, M., & Gustafsson, J.-Å. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.133 · Cited by 22
Self-citationGustafsson, J.-A. (2005) · Molecular Endocrinology · doi:10.1210/me.2004-0479 · Cited by 19
Self-citationThe Role of Lipid Bodies in the Microglial Aging Process and Related Diseases
Hu, X., Xu, B., & Ge, W. (2017) · Neurochemical Research · doi:10.1007/s11064-017-2351-4 · Cited by 17
Metadata
- Authors
- Wang, L., Schuster, G. U., Hultenby, K., Zhang, Q., Andersson, S., & Gustafsson, J.-Å.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-10-04
- Volume
- 99
- Issue
- 21
- Pages
- 13878-13883
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2080305329
- Cited by
- 286
- References
- 6
- FWCI
- 8.77
- Type
- journal article
- Language
- en
- Open access
- green
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