Liver X Receptors and Their Implications in the Physiology and Pathology of the Peripheral Nervous System

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Aug 30

PMID 31461876

Citations 4

Authors

Venkat Krishnan Sundaram

Charbel Massaad

Julien Grenier

Affiliations

Soon will be listed here.

Abstract

Recent research in the last decade has sought to explore the role and therapeutic potential of Liver X Receptors (LXRs) in the physiology and pathologies of the Peripheral Nervous System. LXRs have been shown to be important in maintaining the redox homeostasis in peripheral nerves for proper myelination, and they regulate ER stress in sensory neurons. Furthermore, LXR stimulation has a positive impact on abrogating the effects of diabetic peripheral neuropathy and obesity-induced allodynia in the Peripheral Nervous System (PNS). This review details these findings and addresses certain important questions that are yet to be answered. The potential roles of LXRs in different cells of the PNS are speculated based on existing knowledge. The review also aims to provide important perspectives for further research in elucidating the role of LXRs and assessing the potential of LXR based therapies to combat pathologies of the Peripheral Nervous System.

Citing Articles

Review: Myelin clearance is critical for regeneration after peripheral nerve injury.

Yuan Y, Wang Y, Wu S, Zhao M Front Neurol. 2023; 13:908148.

PMID: 36588879 PMC: 9801717. DOI: 10.3389/fneur.2022.908148.

Liver X Receptor Regulation of Glial Cell Functions in the CNS.

Song X, Wu W, Warner M, Gustafsson J Biomedicines. 2022; 10(9).

PMID: 36140266 PMC: 9496004. DOI: 10.3390/biomedicines10092165.

Liver X receptor-agonist treatment rescues degeneration in a Drosophila model of hereditary spastic paraplegia.

Byrne D, Garcia-Pardo M, Cole N, Batnasan B, Heneghan S, Sohail A Acta Neuropathol Commun. 2022; 10(1):40.

PMID: 35346366 PMC: 8961908. DOI: 10.1186/s40478-022-01343-6.

Association between LXR- and ABCA1 Gene Polymorphisms and the Risk of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus in a Chinese Han Population.

Liu P, Ma L, Zhao H, Shen Z, Zhou X, Yan M J Diabetes Res. 2021; 2020:8721536.

PMID: 33426085 PMC: 7772016. DOI: 10.1155/2020/8721536.

References

Parmantier E, Lynn B, Lawson D, Turmaine M, Namini S, Chakrabarti L . Schwann cell-derived Desert hedgehog controls the development of peripheral nerve sheaths. Neuron. 1999; 23(4):713-24. DOI: 10.1016/s0896-6273(01)80030-1. View

REPA J, Liang G, Ou J, Bashmakov Y, Lobaccaro J, Shimomura I . Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev. 2000; 14(22):2819-30. PMC: 317055. DOI: 10.1101/gad.844900. View

Alberti S, Schuster G, Parini P, Feltkamp D, Diczfalusy U, Rudling M . Hepatic cholesterol metabolism and resistance to dietary cholesterol in LXRbeta-deficient mice. J Clin Invest. 2001; 107(5):565-73. PMC: 199420. DOI: 10.1172/JCI9794. View

Zhang Y, REPA J, Gauthier K, Mangelsdorf D . Regulation of lipoprotein lipase by the oxysterol receptors, LXRalpha and LXRbeta. J Biol Chem. 2001; 276(46):43018-24. DOI: 10.1074/jbc.M107823200. View

Wang L, Schuster G, Hultenby K, Zhang Q, Andersson S, Gustafsson J . Liver X receptors in the central nervous system: from lipid homeostasis to neuronal degeneration. Proc Natl Acad Sci U S A. 2002; 99(21):13878-83. PMC: 129791. DOI: 10.1073/pnas.172510899. View

Valentijn L, Bolhuis P, Zorn I, Hoogendijk J, Van Den Bosch N, Hensels G . The peripheral myelin gene PMP-22/GAS-3 is duplicated in Charcot-Marie-Tooth disease type 1A. Nat Genet. 1992; 1(3):166-70. DOI: 10.1038/ng0692-166. View

Joseph N, Mukouyama Y, Mosher J, Jaegle M, Crone S, Dormand E . Neural crest stem cells undergo multilineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells. Development. 2004; 131(22):5599-612. PMC: 2638001. DOI: 10.1242/dev.01429. View

Andersson S, Gustafsson N, Warner M, Gustafsson J . Inactivation of liver X receptor beta leads to adult-onset motor neuron degeneration in male mice. Proc Natl Acad Sci U S A. 2005; 102(10):3857-62. PMC: 553330. DOI: 10.1073/pnas.0500634102. View

Jessen K, Mirsky R . The origin and development of glial cells in peripheral nerves. Nat Rev Neurosci. 2005; 6(9):671-82. DOI: 10.1038/nrn1746. View

10.

Lund E, Peterson L, Adams A, Lam M, Burton C, Chin J . Different roles of liver X receptor alpha and beta in lipid metabolism: effects of an alpha-selective and a dual agonist in mice deficient in each subtype. Biochem Pharmacol. 2005; 71(4):453-63. DOI: 10.1016/j.bcp.2005.11.004. View

11.

Melcangi R, Panzica G . Neuroactive steroids: old players in a new game. Neuroscience. 2005; 138(3):733-9. DOI: 10.1016/j.neuroscience.2005.10.066. View

12.

Sharghi-Namini S, Turmaine M, Meier C, Sahni V, Umehara F, Jessen K . The structural and functional integrity of peripheral nerves depends on the glial-derived signal desert hedgehog. J Neurosci. 2006; 26(23):6364-76. PMC: 6675191. DOI: 10.1523/JNEUROSCI.0157-06.2006. View

13.

Muller M, Stenner M, Wacker K, Ringelstein E, Hickey W, Kiefer R . Contribution of resident endoneurial macrophages to the local cellular response in experimental autoimmune neuritis. J Neuropathol Exp Neurol. 2006; 65(5):499-507. DOI: 10.1097/01.jnen.0000229239.43866.d1. View

14.

Melcangi R, Garcia-Segura L . Therapeutic approaches to peripheral neuropathy based on neuroactive steroids. Expert Rev Neurother. 2006; 6(8):1121-5. DOI: 10.1586/14737175.6.8.1121. View

15.

Melcangi R, Garcia-Segura L, Mensah-Nyagan A . Neuroactive steroids: state of the art and new perspectives. Cell Mol Life Sci. 2007; 65(5):777-97. PMC: 11131680. DOI: 10.1007/s00018-007-7403-5. View

16.

Johansson G, Mahller Y, Collins M, Kim M, Nobukuni T, Perentesis J . Effective in vivo targeting of the mammalian target of rapamycin pathway in malignant peripheral nerve sheath tumors. Mol Cancer Ther. 2008; 7(5):1237-45. PMC: 2855168. DOI: 10.1158/1535-7163.MCT-07-2335. View

17.

Higuchi N, Kato M, Shundo Y, Tajiri H, Tanaka M, Yamashita N . Liver X receptor in cooperation with SREBP-1c is a major lipid synthesis regulator in nonalcoholic fatty liver disease. Hepatol Res. 2008; 38(11):1122-9. DOI: 10.1111/j.1872-034X.2008.00382.x. View

18.

Woodhoo A, Sommer L . Development of the Schwann cell lineage: from the neural crest to the myelinated nerve. Glia. 2008; 56(14):1481-1490. DOI: 10.1002/glia.20723. View

19.

Gabbi C, Warner M, Gustafsson J . Minireview: liver X receptor beta: emerging roles in physiology and diseases. Mol Endocrinol. 2008; 23(2):129-36. PMC: 5419308. DOI: 10.1210/me.2008-0398. View

20.

Saher G, Quintes S, Mobius W, Wehr M, Kramer-Albers E, Brugger B . Cholesterol regulates the endoplasmic reticulum exit of the major membrane protein P0 required for peripheral myelin compaction. J Neurosci. 2009; 29(19):6094-104. PMC: 6665514. DOI: 10.1523/JNEUROSCI.0686-09.2009. View