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| The role of LXRs in the pathogenesis of Alzheimer's disease: a review |
| LIU Heqiong1,2, MA Chaoying1,2, GUO Huicai1,2, WANG Lei3, LIU Yi1,2
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1. School of Public Health, Hebei Medical University, Shijiazhuang, Hebei 050017, China;
2. Hebei Key Laboratory of Environment and Human Health, Shijiazhuang, Hebei 050017, China;
3. Hebei Medical University, Shijiazhuang, Hebei 050017, China |
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Abstract Alzheimer's disease (AD) is a neurodegenerative disease characterized by deposition of β-amyloid (Aβ). Liver X receptors (LXRs), a member of the nuclear receptor transcription factor superfamily, are widely expressed in brain, which may be involved in the development and progression of AD. Based on the international and national publications pertaining to the association between LXRs and AD from 2010 to 2022, this review summarizes the advances on the involvement of LXRs in the regulation of cholesterol metabolism, inflammatory response and synapse formation in the pathogenesis of AD was reviewed, so as to provide insights into the prevention and treatment of AD.
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Received: 01 September 2022
Revised: 17 January 2023
Published: 17 March 2023
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[1] VILLAIN N,DUBOIS B.Alzheimer's disease including focal presentations[J].Semin Neurol,2019,39(2):213-226.
[2] KANG J,RIVEST S.Lipid metabolism and neuroinflammation in Alzheimer's disease:a role for liver X receptors[J].Endocr Rev,2012,33(5):715-746.
[3] 韩汶润,张丹丹,朱彦,等.肝X受体调控脂代谢研究进展[J].中国药理学与毒理学杂志,2021,35(5):10.
[4] CUI W,SUN Y,WANG Z,et al.Liver X receptor activation attenuates inflammatory response and protects cholinergic neurons in APP/PS1 transgenic mice[J].Neuroscience,2012,210:200-210.
[5] NA Y,KE L,JIE Z,et al.Amelioration of cholesterol rich diet-induced impaired cognition in AD transgenic mice by an LXR Agonist TO901317 is associated with the activation of the LXR-β-RXR-α-ABCA1 transmembrane transport system and improving the composition of lipid raft[J/OL].Exp Aging Res,2022[2023-01-17].https://doi.org/10.1080/0361073X.2022.2095605.
[6] CHIANG M C,NICOL C J B,CHEN S J,et al.TO901317 activation of LXR-dependent pathways mitigate amyloid-beta peptide-induced neurotoxicity in 3D human neural stem cell culture scaffolds and AD mice[J].Brain Res Bull,2022,178:57-68.
[7] UDDIN M,KABIR M,AL MAMUN A,et al.ApoE and Alzheimer's disease:evidence mounts that targeting ApoE4 may combat Alzheimer's pathogenesis[J].Mol Neurobiol,2019,56(4):2450-2465.
[8] RAWAT V,WANG S,SIMA J,et al.ApoE4 alters ABCA1 membrane trafficking in astrocytes[J].J Neurosci,2019,39(48):9611-9622.
[9] HAN M,WANG S,YANG N,et al.Therapeutic implications of altered cholesterol homeostasis mediated by loss of CYP46A1 in human glioblastoma[J/OL].EMBO Mol Med,2020,12(1)[2023-01-17].https://doi.org/10.15252/emmm.201910924.
[10] ZHAO Y,HU D,WANG R,et al.ATAD3A oligomerization promotes neuropathology and cognitive deficits in Alzheimer's disease models[J/OL].Nat Commun,2022,13(1)[2023-01-17].https://doi.org/10.1038/s41467-022-28769-9.
[11] RUDGE J D.A new hypothesis for Alzheimer's disease:the lipid invasion mode[J].J Alzheimers Dis Rep,2022,6(1):129-161.
[12] MAHLEY R W.Central nervous system lipoproteins:ApoE and regulation of cholesterol metabolism[J].Arterioscler Thromb Vasc Biol,2016,36(7):1305-1315.
[13] DI PAOLO G,KIM T W.Linking lipids to Alzheimer's disease:cholesterol and beyond[J].Nat Rev Cancer,2011,12(5):284-296.
[14] HABCHI J,CHIA S,GALVAGNION C,et al.Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes[J].Nat Chem,2018,10(6):673-683.
[15] 崔卫刚. 激活LXR通过减少膜胆固醇含量下调β-分泌酶活性[D].上海:复旦大学,2011.
[16] PATERNITI I,CAMPOLO M,SIRACUSA R,et al.Liver X receptors activation,through TO901317 binding,reduces neuroinflammation in Parkinson's disease[J/OL].PLoS One,2017,12(4)[2023-01-17].https://doi.org/10.1371/journal.pone.0174470.
[17] 崔卫刚,彭裕文,李瑞锡.肝X受体激活剂抑制APP/PS1转基因AD小鼠脑内炎症反应[C]//中国解剖学会.中国解剖学会2012年年会论文文摘汇编.上海:解剖学杂志编辑部,2012:78.
[18] FESSLER M B .The challenges and promise of targeting the liver X receptors for treatment of inflammatory disease[J/OL].Pharmacol Ther,2018,181[2023-01-17].https://doi.org/10.1016/j.pharmthera.2017.07.010.
[19] ZELCER N,KHANLOU N,CLARE R,et al.Attenuation of neuroinflammation and Alzheimer's disease pathology by liver X receptors[J].Proc Natl Acad Sci U S A,2007,104(25):10601-10606.
[20] COLONNA M,BUTOVSKY O.Microglia function in the central nervous system during health and neurodegeneration[J].Annu Rev Immunol,2017,35:441-468.
[21] SUBHRAMANYAM C S,WANG C,HU Q,et al.Microglia-mediated neuroinflammation in neurodegenerative diseases[J].Semin Cell Dev Biol,2019,94:112-120.
[22] 李静,祝佩林,黎悦,等.肝X受体激动剂GW3965对应激小鼠海马小胶质细胞活化的影响[J].神经解剖学杂志,2022,38(2):163-170.
[23] 高碧聪,陈泉,孙婷,等.肝X受体与炎症相关疾病关系的研究进展[J].生理学报,2018,70(3):335-341.
[24] XU X,XIAO X,YAN Y,et al.Activation of liver X receptors prevents emotional and cognitive dysfunction by suppressing microglial M1-polarization and restoring synaptic plasticity in the hippocampus of mice[J].Brain Behav Immun,2021,94:111-124.
[25] DAYALAN S,MONICA S,SAMUEL N.Cognitive dysfunction in major depression and Alzheimer's disease is associated with hippocampal-prefrontal cortex dysconnectivity[J].Neuropsychiatr Dis Treat,2017,13:1509-1519.
[26] CHEN J,ZACHAREK A,CUI X,et al.Treatment of stroke with a synthetic liver X receptor agonist,TO901317,promotes synaptic plasticity and axonal regeneration in mice[J].J Cereb Blood Flow Metab,2010,30(1):102-109.
[27] CUI X,CHOPP M,ZACHAREK A,et al.The neurorestorative benefit of GW3965 treatment of stroke in mice[J].Stroke,2013,44(1):153-161.
[28] BÁEZ-BECERRA C,FILIPELLO F,SANDOVAL-HERNÁNDEZ A,et al.Liver X receptor agonist GW3965 regulates synaptic function upon amyloid beta exposure in hippocampal neurons[J].Neurotox Res,2018,33(3):569-579. |
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