Abstract
Peroxidase proliferator receptors (PPARs) are defined as key sensors and regulators of cell metabolism, transcription factors activated by ligands, involved in lipid, glucose and amino acid metabolism, participating in the processes of cell differentiation, apoptosis, inflammation regulation, and acute and chronic nerve damage. Among them, PPARγ is expressed in different brain regions and can regulate lipid metabolism, mitochondrial disorders, oxidative stress, and cell apoptosis. It has anti-inflammatory activity and shows neuroprotection. The regulation of Aβ levels in Alzheimer’s disease involves cholesterol metabolism and inflammation, so this article first analyzes the biological functions of PPARγ, then mainly focuses on the relationship between cholesterol and inflammation and Aβ, and elaborates on the regulation of PPARγ on key proteins and the corresponding molecules, which provides new ideas for the treatment of AD.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
Not applicable.
Code availability (software application or custom code)
Not applicable.
References
Ahn D, Kim J, Nam G, Zhao X, Kwon J, Hwang JY, . . . Chung SJ (2022) Ethyl gallate dual-targeting PTPN6 and PPARγ shows anti-diabetic and anti-obese effects. Int J Mol Sci 23(9). Retrieved from https://mdpi-res.com/d_attachment/ijms/ijms-23-05020/article_deploy/ijms-23-05020-v2.pdf?version=1651736266, https://doi.org/10.3390/ijms23095020
Assaf N, El-Shamarka ME, Salem NA, Khadrawy YA, El Sayed NS (2020) Neuroprotective effect of PPAR alpha and gamma agonists in a mouse model of amyloidogenesis through modulation of the Wnt/beta catenin pathway via targeting alpha- and beta-secretases. Prog Neuropsychopharmacol Biol Psychiatry 97:109793. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31669201, https://doi.org/10.1016/j.pnpbp.2019.109793
Bacchetti T, Vignini A, Giulietti A, Nanetti L, Provinciali L, Luzzi S, . . . Ferretti G (2015) Higher levels of oxidized low density lipoproteins in alzheimer's disease patients: roles for platelet activating factor acetyl hydrolase and paraoxonase-1. J Alzheimers Dis 46(1):179–186. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25720407, https://doi.org/10.3233/JAD-143096
Badana AK, Chintala M, Gavara MM, Naik S, Kumari S, Kappala VR, . . . Malla RR (2018) Lipid rafts disruption induces apoptosis by attenuating expression of LRP6 and survivin in triple negative breast cancer. Biomed Pharmacother 97:359–368. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/29091885, https://doi.org/10.1016/j.biopha.2017.10.045
Bedir A, Aliyazicioglu Y, Kahraman H, Yurdakul Z, Uysal M, Suvaci DE, . . . Alvur M (2006) Genotoxicity in rats treated with the antidiabetic agent, rosiglitazone. Environ Mol Mutagen 47(9):718–724. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17078099, https://doi.org/10.1002/em.20261
Beetz A, Peter RU, Oppel T, Kaffenberger W, Rupec RA, Meyer M, . . . Messer G (2000) NF-kappaB and AP-1 are responsible for inducibility of the IL-6 promoter by ionizing radiation in HeLa cells. Int J Radiat Biol 76(11):1443–1453. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11098847, https://doi.org/10.1080/09553000050176207
Bhalla K, Hwang BJ, Choi JH, Dewi R, Ou L, McLenithan J, . . . Girnun GD (2011) N-Acetylfarnesylcysteine is a novel class of peroxisome proliferator-activated receptor γ ligand with partial and full agonist activityin vitroandin vivo. J Biol Chem 286(48):41626-41635. https://doi.org/10.1074/jbc.M111.257915
Bilousova T, Melnik M, Miyoshi E, Gonzalez BL, Poon WW, Vinters HV, . . . Gylys KH (2019) Apolipoprotein E/Amyloid-beta complex accumulates in alzheimer disease cortical synapses via apolipoprotein E receptors and is enhanced by APOE4. Am J Pathol 189(8):1621–1636. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31108099, https://doi.org/10.1016/j.ajpath.2019.04.010
Birch AM (2014) The contribution of astrocytes to Alzheimer’s disease. Biochem Soc Trans 42(5):1316–1320. Retrieved from https://portlandpress.com/biochemsoctrans/article-abstract/42/5/1316/64698/The-contribution-of-astrocytes-to-Alzheimer-s?redirectedFrom=fulltext, https://doi.org/10.1042/bst20140171
Bourré G, Cantrelle FX, Kamah A, Chambraud B, Landrieu I, Smet-Nocca C (2018) Direct crosstalk between O-GlcNAcylation and phosphorylation of Tau protein investigated by NMR spectroscopy. Front Endocrinol (Lausanne) 9:595. https://doi.org/10.3389/fendo.2018.00595
Braidy N., Zarka M, Jugder BE., Welch J, Jayasena T, Chan DKY, . . . Bridge W (2019) The Precursor to Glutathione (GSH), gamma-Glutamylcysteine (GGC), can ameliorate oxidative damage and neuroinflammation induced by Abeta40 oligomers in human astrocytes. Front Aging Neurosci 11:177. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31440155, https://doi.org/10.3389/fnagi.2019.00177
Brodbeck J, Balestra ME, Saunders AM, Roses AD, Mahley RW, Huang Y (2008) Rosiglitazone increases dendritic spine density and rescues spine loss caused by apolipoprotein E4 in primary cortical neurons. Proc Natl Acad Sci U S A 105(4):1343–1346. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18212130, https://doi.org/10.1073/pnas.0709906104
Bruning JB, Chalmers MJ, Prasad S, Busby SA, Kamenecka TM, He Y, . . . Griffin PR (2007) Partial agonists activate PPARgamma using a helix 12 independent mechanism. Structure 15(10):1258–1271. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17937915, https://doi.org/10.1016/j.str.2007.07.014
Buxbaum JD, Oishi M, Chen HI, Pinkas-Kramarski R, Jaffe EA, Gandy SE, Greengard P (1992) Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer beta/A4 amyloid protein precursor. Proc Natl Acad Sci U S A 89(21):10075–10078. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1359534, https://doi.org/10.1073/pnas.89.21.10075
Cascella R, Evangelisti E, Bigi A, Becatti M, Fiorillo C, Stefani M, . . . Cecchi C (2017) Soluble oligomers require a ganglioside to trigger neuronal calcium overload. J Alzheimers Dis 60(3):923–938. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/28922156, https://doi.org/10.3233/JAD-170340
Cekmen N, Cesur M, Cetinbas R, Bedel P, Erdemli O (2006) Acute pulmonary edema due to rosiglitazone use in a patient with diabetes mellitus. J Intensive Care Med 21(1):47–50. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16698744, https://doi.org/10.1177/0885066605283385
Chang H, Di T, Wang Y, Zeng X, Li G, Wan Q, . . . Chen L (2019) Seipin deletion in mice enhances phosphorylation and aggregation of tau protein through reduced neuronal PPARgamma and insulin resistance. Neurobiol Dis 127:350–361. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/30910747, https://doi.org/10.1016/j.nbd.2019.03.023
Chen SY, Chen TF, Lai LC, Chen JH, Sun Y, Wen LL, . . . Chen YC (2012) Sequence variants of interleukin 6 (IL-6) are significantly associated with a decreased risk of late-onset Alzheimer's disease. J Neuroinflammation 9:21. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315433/pdf/1742-2094-9-21.pdf, https://doi.org/10.1186/1742-2094-9-21
Cho YY, Kwon OH, Park MK, Kim TW, Chung S (2019) Elevated cellular cholesterol in Familial Alzheimer’s presenilin 1 mutation is associated with lipid raft localization of beta-amyloid precursor protein. PLoS One 14(1):e0210535. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30682043, https://doi.org/10.1371/journal.pone.0210535
Corona AW, Kodoma N, Casali BT, Landreth GE (2016) ABCA1 is necessary for Bexarotene-Mediated clearance of soluble Amyloid Beta from the Hippocampus of APP/PS1 Mice. J Neuroimmune Pharmacol 11(1):61–72. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558963/pdf/nihms-985839.pdf, https://doi.org/10.1007/s11481-015-9627-8
Corona JC, Duchen MR (2016) PPARgamma as a therapeutic target to rescue mitochondrial function in neurological disease. Free Radic Biol Med 100:153–163. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/27352979, https://doi.org/10.1016/j.freeradbiomed.2016.06.023
Croitoru-Lamoury J, Guillemin GJ, Boussin FD, Mognetti B, Gigout LI, Chéret A, . . . Dormont D (2003) Expression of chemokines and their receptors in human and simian astrocytes: evidence for a central role of TNF alpha and IFN gamma in CXCR4 and CCR5 modulation. Glia 41(4):354–370. Retrieved from https://onlinelibrary.wiley.com/doi/10.1002/glia.10181, https://doi.org/10.1002/glia.10181
Cui W, Sun C, Ma Y, Wang S, Wang X, Zhang Y (2020) Inhibition of TLR4 Induces M2 Microglial Polarization and Provides Neuroprotection via the NLRP3 Inflammasome in Alzheimer’s Disease. Front Neurosci 14:444. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/32508567, https://doi.org/10.3389/fnins.2020.00444
Dafnis I, Raftopoulou C, Mountaki C, Megalou E, Zannis VI, Chroni A (2018) ApoE isoforms and carboxyl-terminal-truncated apoE4 forms affect neuronal BACE1 levels and Abeta production independently of their cholesterol efflux capacity. Biochem J 475(10):1839–1859. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/29743204, https://doi.org/10.1042/BCJ20180068
Dana N, Vaseghi G, Haghjooy Javanmard S (2019) PPAR gamma agonist, pioglitazone, suppresses melanoma cancer in mice by inhibiting TLR4 signaling. J Pharm Pharm Sci 22(1):418–423. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31509504, https://doi.org/10.18433/jpps30626
Delint-Ramirez I, Salcedo-Tello P, Bermudez-Rattoni F (2008) Spatial memory formation induces recruitment of NMDA receptor and PSD-95 to synaptic lipid rafts. J Neurochem 106(4):1658–1668. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18700282, https://doi.org/10.1111/j.1471-4159.2008.05523.x
Deng Y, Jiang X, Deng X, Chen H, Xu J, Zhang Z, . . . Wang C (2020) Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPARgamma/NF-kappaB/IL-6 signaling pathway. Genes Dis 7(2):253–265. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/32215295, https://doi.org/10.1016/j.gendis.2019.05.002
DiBattista AM, Dumanis SB, Newman J, Rebeck GW (2016) Identification and modification of amyloid-independent phenotypes of APOE4 mice. Exp Neurol 280:97–105. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/27085394, https://doi.org/10.1016/j.expneurol.2016.04.014
Doens D, Valiente PA, Mfuh AM, AXTV, Tristan A, Carreno L, . . . Fernandez PL (2017) Identification of inhibitors of CD36-Amyloid beta binding as potential agents for alzheimer's disease. ACS Chem Neurosci 8(6):1232–1241. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/28150942, https://doi.org/10.1021/acschemneuro.6b00386
Dong Y, Yu H, Li X, Bian K, Zheng Y, Dai M, . . . Kong W (2022) Hyperphosphorylated tau mediates neuronal death by inducing necroptosis and inflammation in Alzheimer's disease. J Neuroinflammation 19(1):205. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377071/pdf/12974_2022_Article_2567.pdf, https://jneuroinflammation.biomedcentral.com/counter/pdf/10.1186/s12974-022-02567-y.pdf, https://doi.org/10.1186/s12974-022-02567-y
Dunn FL, Higgins LS, Fredrickson J, DePaoli AM, group INTs (2011) Selective modulation of PPARgamma activity can lower plasma glucose without typical thiazolidinedione side-effects in patients with Type 2 diabetes. J Diabetes Complications 25(3):151–158. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20739195, https://doi.org/10.1016/j.jdiacomp.2010.06.006
Elliott C, Rojo AI, Ribe E, Broadstock M, Xia W, Morin P, . . . Killick R (2018) A role for APP in Wnt signalling links synapse loss with beta-amyloid production. Transl Psychiatry 8(1):179. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30232325, https://doi.org/10.1038/s41398-018-0231-6
Feng J, Han J, Pearce SF, Silverstein RL, Gotto AM Jr, Hajjar DP, Nicholson AC (2000) Induction of CD36 expression by oxidized LDL and IL-4 by a common signaling pathway dependent on protein kinase C and PPAR-gamma. J Lipid Res 41(5):688–696. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10787429
Fernandez-Lizarbe S, Pascual M, Gascon MS, Blanco A, Guerri C (2008) Lipid rafts regulate ethanol-induced activation of TLR4 signaling in murine macrophages. Mol Immunol 45(7):2007–2016. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18061674, https://doi.org/10.1016/j.molimm.2007.10.025
Fu Y, Xin Z, Liu B, Wang J, Wang J, Zhang X, . . . Li F (2017) Platycodin D inhibits inflammatory response in LPS-Stimulated primary rat microglia cells through activating LXRalpha-ABCA1 signaling pathway. Front Immunol 8:1929. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/29375565, https://doi.org/10.3389/fimmu.2017.01929
Fujioka H, Phelix CF, Friedland RP, Zhu X, Perry EA, Castellani RJ, Perry G (2013) Apolipoprotein E4 prevents growth of malaria at the intraerythrocyte stage: implications for differences in racial susceptibility to Alzheimer’s disease. J Health Care Poor Underserved 24(4 Suppl):70–78. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24241262, https://doi.org/10.1353/hpu.2014.0009
Gad ES, Zaitone SA, Moustafa YM (2016) Pioglitazone and exenatide enhance cognition and downregulate hippocampal beta amyloid oligomer and microglia expression in insulin-resistant rats. Can J Physiol Pharmacol 94(8):819–828. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/27389824, https://doi.org/10.1139/cjpp-2015-0242
Gherardelli C, Cisternas P, Vera-Salazar RF, Mendez-Orellana C, Inestrosa NC (2022) Age- and sex-associated glucose metabolism decline in a mouse model of alzheimer’s disease. J Alzheimers Dis 87(2):901–917. Retrieved from https://content.iospress.com/articles/journal-of-alzheimers-disease/jad215273, https://doi.org/10.3233/jad-215273
Goldgaber D, Harris HW, Hla T, Maciag T, Donnelly RJ, Jacobsen JS, . . . Gajdusek DC (1989) Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. Proc Natl Acad Sci U S A 86(19):7606–7610. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/2508093, https://doi.org/10.1073/pnas.86.19.7606
Gong P, Zhang W, Zou C, Han S, Tian Q, Wang J, . . . Li M (2022) Andrographolide attenuates blood-brain barrier disruption, neuronal apoptosis, and oxidative stress through activation of Nrf2/HO-1 signaling pathway in subarachnoid hemorrhage. Neurotox Res 40(2):508–519. Retrieved from https://link.springer.com/article/10.1007/s12640-022-00486-7, https://doi.org/10.1007/s12640-022-00486-7
Guo C, Ma R, Liu X, Chen T, Li Y, Yu Y, . . . Sun Z (2018) Silica nanoparticles promote oxLDL-induced macrophage lipid accumulation and apoptosis via endoplasmic reticulum stress signaling. Sci Total Environ 631–632:570–579. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/29533793, https://doi.org/10.1016/j.scitotenv.2018.02.312
Guo J, Liang W, Li J, Long J (2016) Knockdown of FSTL1 inhibits oxLDL-induced inflammation responses through the TLR4/MyD88/NF-kappaB and MAPK pathway. Biochem Biophys Res Commun 478(4):1528–1533. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/27569284, https://doi.org/10.1016/j.bbrc.2016.08.138
Han T, Lv Y, Wang S, Hu T, Hong H, Fu Z (2019) PPARgamma overexpression regulates cholesterol metabolism in human L02 hepatocytes. J Pharmacol Sci 139(1):1–8. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30554802, https://doi.org/10.1016/j.jphs.2018.09.013
Hazra S, Xiong S, Wang J, Rippe RA, Krishna V, Chatterjee K, Tsukamoto H (2004) Peroxisome proliferator-activated receptor gamma induces a phenotypic switch from activated to quiescent hepatic stellate cells. J Biol Chem 279(12):11392–11401. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/14702344, https://doi.org/10.1074/jbc.M310284200
Heneka MT, Rodríguez JJ, Verkhratsky A (2010) Neuroglia in neurodegeneration. Brain Res Rev 63(1–2):189–211. https://doi.org/10.1016/j.brainresrev.2009.11.004
Hering H, Lin CC, Sheng M (2003) Lipid rafts in the maintenance of synapses, dendritic spines, and surface AMPA receptor stability. J Neurosci 23(8):3262–3271. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12716933
Hong OY, Youn HJ, Jang HY, Jung SH, Noh EM, Chae HS, . . . Kim, JS (2018) Troglitazone inhibits matrix Metalloproteinase-9 expression and invasion of breast cancer cell through a peroxisome proliferator-activated receptor gamma-dependent mechanism. J Breast Cancer 21(1):28–36. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/29628981, https://doi.org/10.4048/jbc.2018.21.1.28
Hossain R, Quispe C, Herrera-Bravo J, Beltrán JF, Islam MT, Shaheen S, . . . Cho WC (2022) Neurobiological promises of the bitter diterpene lactone andrographolide. Oxid Med Cell Longev 2022:3079577. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8825670/pdf/OMCL2022-3079577.pdf, https://doi.org/10.1155/2022/3079577
Hou Y, Moreau F, Chadee K (2012) PPARgamma is an E3 ligase that induces the degradation of NFkappaB/p65. Nat Commun 3:1300. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/23250430, https://doi.org/10.1038/ncomms2270
Huang X, Lv Y, He P, Wang Z, Xiong F, He L, . . . Tang C (2018) HDL impairs osteoclastogenesis and induces osteoclast apoptosis via upregulation of ABCG1 expression. Acta Biochim Biophys Sin (Shanghai) 50(9):853–861. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30060101, https://doi.org/10.1093/abbs/gmy081
Huang Z, Liang N, Damdimopoulos A, Fan R, Treuter E (2019) G protein pathway suppressor 2 (GPS2) links inflammation and cholesterol efflux by controlling lipopolysaccharide-induced ATP-binding cassette transporter A1 expression in macrophages. Faseb J 33(2):1631–1643. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30153049, https://doi.org/10.1096/fj.201801123R
Inoue M, Tanabe H, Matsumoto A, Takagi M, Umegaki K, Amagaya S, Takahashi J (2012) Astaxanthin functions differently as a selective peroxisome proliferator-activated receptor gamma modulator in adipocytes and macrophages. Biochem Pharmacol 84(5):692–700. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22732454, https://doi.org/10.1016/j.bcp.2012.05.021
Jeon M, Rahman N, Kim YS (2016) Wnt/beta-catenin signaling plays a distinct role in methyl gallate-mediated inhibition of adipogenesis. Biochem Biophys Res Commun 479(1):22–27. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/27592552, https://doi.org/10.1016/j.bbrc.2016.08.178
Jeon Y, Jung Y, Youm J-K, Kang KS, Kim YK, Kim S-N (2015) Abietic acid inhibits UVB-induced MMP-1 expression in human dermal fibroblast cells through PPARα/γdual activation. Exp Dermatol 24(2):140–145. https://doi.org/10.1111/exd.12616
Johnson TB, Cain JT, White KA, Ramirez-Montealegre D, Pearce DA, Weimer JM (2019) Therapeutic landscape for Batten disease: current treatments and future prospects. Nat Rev Neurol 15(3):161–178. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/30783219, https://doi.org/10.1038/s41582-019-0138-8
Keller JN, Hanni KB, Markesbery WR (1999) Oxidized low-density lipoprotein induces neuronal death: implications for calcium, reactive oxygen species, and caspases. J Neurochem 72(6):2601–2609. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10349872, https://doi.org/10.1046/j.1471-4159.1999.0722601.x
Kelly D, Campbell JI, King TP, Grant G, Jansson EA, Coutts AG, . . . Conway S (2004) Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA. Nat Immunol 5(1):104–112. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/14691478, https://doi.org/10.1038/ni1018
Kim HJ, Moon JH, Kim HM, Yun MR, Jeon BH, Lee B, . . . Cha BS (2014) The hypolipidemic effect of cilostazol can be mediated by regulation of hepatic low-density lipoprotein receptor-related protein 1 (LRP1) expression. Metabolism 63(1):112–119. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/24139096, https://doi.org/10.1016/j.metabol.2013.09.006
Kirouac L, Rajic AJ, Cribbs DH, Padmanabhan J (2017) Activation of Ras-ERK signaling and GSK-3 by amyloid precursor protein and Amyloid Beta facilitates neurodegeneration in alzheimer's disease. eNeuro 4(2). Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/28374012, https://doi.org/10.1523/ENEURO.0149-16.2017
Koseki M, Hirano K, Masuda D, Ikegami C, Tanaka M, Ota A, . . . Yamashita S (2007) Increased lipid rafts and accelerated lipopolysaccharide-induced tumor necrosis factor-alpha secretion in Abca1-deficient macrophages. J Lipid Res 48(2):299–306. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17079792, https://doi.org/10.1194/jlr.M600428-JLR200
Lasič E, Galland F, Vardjan N, Šribar J, Križaj I, Leite MC, . . . Stenovec M (2016) Time-dependent uptake and trafficking of vesicles capturing extracellular S100B in cultured rat astrocytes. J Neurochem 139(2):309–323. Retrieved from https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jnc.13754?download=true, https://doi.org/10.1111/jnc.13754
Lazarenko OP, Rzonca SO, Hogue WR, Swain FL, Suva LJ, Lecka-Czernik B (2007) Rosiglitazone induces decreases in bone mass and strength that are reminiscent of aged bone. Endocrinology 148(6):2669–2680. https://doi.org/10.1210/en.2006-1587
Lee HT, Lee KI, Chen CH, Lee TS (2019a) Genetic deletion of soluble epoxide hydrolase delays the progression of Alzheimer’s disease. J Neuroinflammation 16(1):267. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31847859, https://doi.org/10.1186/s12974-019-1635-9
Lee Y, Kim S, Oh Y, Kim YM, Chin YW, Cho J (2019b) Inhibition of oxidative neurotoxicity and scopolamine-induced memory impairment by gamma-Mangostin: In vitro and in vivo evidence. Oxid Med Cell Longev 2019:3640753. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31019651, https://doi.org/10.1155/2019/3640753
Lefterov I, Wolfe CM, Fitz NF, Nam KN, Letronne F, Biedrzycki RJ, . . . Koldamova R (2019) APOE2 orchestrated differences in transcriptomic and lipidomic profiles of postmortem AD brain. Alzheimers Res Ther 11(1):113. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31888770, https://doi.org/10.1186/s13195-019-0558-0
Li C, Zhao R, Gao K, Wei Z, Yin MY, Lau LT, . . . Yu AC (2011) Astrocytes: implications for neuroinflammatory pathogenesis of Alzheimer's disease. Curr Alzheimer Res 8(1):67–80. Retrieved from https://www.eurekaselect.com/article/32495, https://doi.org/10.2174/156720511794604543
Lin SY, Lin KJ, Lin PC, Huang CC, Chang CC, Lee YC, . . . Wang PN (2019) Plasma amyloid assay as a pre-screening tool for amyloid positron emission tomography imaging in early stage Alzheimer's disease. Alzheimers Res Ther 11(1):111. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31881963, https://doi.org/10.1186/s13195-019-0566-0
Liu C-C, Kanekiyo T, Xu H, Bu G (2013) Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol 9(2):106–118. https://doi.org/10.1038/nrneurol.2012.263
Liu CC, Hu J, Zhao N, Wang J, Wang N, Cirrito JR, . . . Bu G (2017) Astrocytic LRP1 mediates brain abeta clearance and impacts amyloid deposition. J Neurosci 37(15):4023–4031. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/28275161, https://doi.org/10.1523/JNEUROSCI.3442-16.2017
Liu G, Chen N, Kaji A, Bode AM, Ryan CA, Dong Z (2001) Proteinase inhibitors I and II from potatoes block UVB-induced AP-1 activity by regulating the AP-1 protein compositional patterns in JB6 cells. Proc Natl Acad Sci U S A 98(10):5786–5791. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11331771, https://doi.org/10.1073/pnas.101116298
Liu Q, Trotter J, Zhang J, Peters MM, Cheng H, Bao J, . . . Bu G (2010) Neuronal LRP1 knockout in adult mice leads to impaired brain lipid metabolism and progressive, age-dependent synapse loss and neurodegeneration. J Neurosci 30(50):17068–17078. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21159977, https://doi.org/10.1523/JNEUROSCI.4067-10.2010
Liu Y, Dai Y, Li Q, Chen C, Chen H, Song Y, . . . Zhang Z (2020) Beta-amyloid activates NLRP3 inflammasome via TLR4 in mouse microglia. Neurosci Lett 736:135279. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/32726591, https://doi.org/10.1016/j.neulet.2020.135279
Luo Y, Wang L, Lv Y, Wu X, Hou C, Li J (2020) Regulation mechanism of silkworm pupa oil PUFAs on cholesterol metabolism in hepatic cell L-02. J Sci Food Agric 100(4):1418–1425. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31667852, https://doi.org/10.1002/jsfa.10115
Ma L, Dong F, Zaid M, Kumar A, Zha X (2012) ABCA1 protein enhances Toll-like receptor 4 (TLR4)-stimulated interleukin-10 (IL-10) secretion through protein kinase A (PKA) activation. J Biol Chem 287(48):40502–40512. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/23055522, https://doi.org/10.1074/jbc.M112.413245
MacIntyre DA, Lee YS, Migale R, Herbert BR, Waddington SN, Peebles D, . . . Bennett PR (2014) Activator protein 1 is a key terminal mediator of inflammation-induced preterm labor in mice. FASEB J 28(5):2358–2368. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/24497579, https://doi.org/10.1096/fj.13-247783
Mander BA, Dave A, Lui KK, Sprecher KE, Berisha D, Chappel-Farley MG, . . . Benca RM (2022) Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to β-amyloid positivity. Sleep 45(9). Retrieved from https://academic.oup.com/sleep/article-abstract/45/9/zsac135/6603598?redirectedFrom=fulltext, https://doi.org/10.1093/sleep/zsac135
Marchi C, Adorni MP, Caffarra P, Ronda N, Spallazzi M, Barocco F, . . . Zimetti F (2019) ABCA1- and ABCG1-mediated cholesterol efflux capacity of cerebrospinal fluid is impaired in Alzheimer's disease. J Lipid Res 60(8):1449–1456. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31167810, https://doi.org/10.1194/jlr.P091033
Marlow L, Cain M, Pappolla MA, Sambamurti K (2003) Beta-secretase processing of the Alzheimer’s amyloid protein precursor (APP). J Mol Neurosci 20(3):233–239. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/14501002, https://doi.org/10.1385/JMN:20:3:233
Martin V, Fabelo N, Santpere G, Puig B, Marin R, Ferrer I, Diaz M (2010) Lipid alterations in lipid rafts from Alzheimer’s disease human brain cortex. J Alzheimers Dis 19(2):489–502. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20110596, https://doi.org/10.3233/JAD-2010-1242
Meng G, Liu Y, Lou C, Yang H (2010) Emodin suppresses lipopolysaccharide-induced pro-inflammatory responses and NF-κB activation by disrupting lipid rafts in CD14-negative endothelial cells. Br J Pharmacol 161(7):1628–1644. https://doi.org/10.1111/j.1476-5381.2010.00993.x
Michailidis M, Tata DA, Moraitou D, Kavvadas D, Karachrysafi S, Papamitsou T, . . . Papaliagkas V (2022) Antidiabetic drugs in the treatment of alzheimer's disease. Int J Mol Sci 23(9). Retrieved from https://mdpi-res.com/d_attachment/ijms/ijms-23-04641/article_deploy/ijms-23-04641.pdf?version=1650622036, https://doi.org/10.3390/ijms23094641
Mu Q, Zhu J, Si Y, Chen X, Duan G, Sun S, . . . Yang N (2019) Overexpression of PID1 reduces high density lipoprotein level and functionality in swine. IUBMB Life 71(12):1946–1951. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31339628, https://doi.org/10.1002/iub.2135
Necela BM, Su W, Thompson EA (2008) Toll-like receptor 4 mediates cross-talk between peroxisome proliferator-activated receptor gamma and nuclear factor-kappaB in macrophages. Immunology 125(3):344–358. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18422969, https://doi.org/10.1111/j.1365-2567.2008.02849.x
Nolte RT, Wisely GB, Westin S, Cobb JE, Lambert MH, Kurokawa R, . . . Milburn MV (1998) Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature 395(6698):137–143. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9744270, https://doi.org/10.1038/25931
Ozasa H, Ayaori M, Iizuka M, Terao Y, Uto-Kondo H, Yakushiji E, . . . Ikewaki K (2011) Pioglitazone enhances cholesterol efflux from macrophages by increasing ABCA1/ABCG1 expressions via PPARgamma/LXRalpha pathway: findings from in vitro and ex vivo studies. Atherosclerosis 219(1):141–150. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21862012, https://doi.org/10.1016/j.atherosclerosis.2011.07.113
Page RL 2nd, Gozansky WS, Ruscin JM (2003) Possible heart failure exacerbation associated with rosiglitazone: case report and literature review. Pharmacotherapy 23(7):945–954. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12885108, https://doi.org/10.1592/phco.23.7.945.32721
Park Y, Pham TX, Lee J (2012) Lipopolysaccharide represses the expression of ATP-binding cassette transporter G1 and scavenger receptor class B, type I in murine macrophages. Inflamm Res 61(5):465–472. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22240665, https://doi.org/10.1007/s00011-011-0433-3
Parr C, Mirzaei N, Christian M, Sastre M (2015) Activation of the Wnt/beta-catenin pathway represses the transcription of the beta-amyloid precursor protein cleaving enzyme (BACE1) via binding of T-cell factor-4 to BACE1 promoter. FASEB J 29(2):623–635. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25384422, https://doi.org/10.1096/fj.14-253211
Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC, Perissi V, . . . Glass CK (2005) A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437(7059):759–763. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16127449, https://doi.org/10.1038/nature03988
Pekny M, Pekna M (2014) Astrocyte reactivity and reactive astrogliosis: costs and benefits. Physiol Rev 94(4):1077–1098. https://doi.org/10.1152/physrev.00041.2013
Ponce J, de la Ossa NP, Hurtado O, Millan M, Arenillas JF, Davalos A, Gasull T (2008) Simvastatin reduces the association of NMDA receptors to lipid rafts: a cholesterol-mediated effect in neuroprotection. Stroke 39(4):1269–1275. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18323503, https://doi.org/10.1161/STROKEAHA.107.498923
Prasad H, Rao R (2018) Amyloid clearance defect in ApoE4 astrocytes is reversed by epigenetic correction of endosomal pH. Proceedings of the National Academy of Sciences of the United States of America 115(28):E6640–E6649. https://doi.org/10.1073/pnas.1801612115
Qian Y, Yin J, Hong J, Li G, Zhang B, Liu G, . . . Chen L (2016) Neuronal seipin knockout facilitates Abeta-induced neuroinflammation and neurotoxicity via reduction of PPARgamma in hippocampus of mouse. J Neuroinflammation 13(1):145. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/27287266, https://doi.org/10.1186/s12974-016-0598-3
Qu X, Guan P, Han L, Wang Z, Huang X (2021) Levistolide A attenuates alzheimer’s pathology through activation of the PPARgamma pathway. Neurotherapeutics 18(1):326–339. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/33034847, https://doi.org/10.1007/s13311-020-00943-1
Querfurth HW, LaFerla FM (2010) Alzheimer’s disease. N Engl J Med 362(4):329–344. https://doi.org/10.1056/NEJMra0909142
Rawat V, Wang S, Sima J, Bar R, Liraz O, Gundimeda U, . . . Yassine HN (2019) ApoE4 alters ABCA1 membrane trafficking in astrocytes. J Neurosci. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31641056, https://doi.org/10.1523/JNEUROSCI.1400-19.2019
Ricote M, Glass CK (2007) PPARs and molecular mechanisms of transrepression. Biochim Biophys Acta 1771(8):926–935. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17433773, https://doi.org/10.1016/j.bbalip.2007.02.013
Riitano G, Manganelli V, Capozzi A, Mattei V, Recalchi S, Martellucci S, . . . Sorice M (2020) LRP6 mediated signal transduction pathway triggered by tissue plasminogen activator acts through lipid rafts in neuroblastoma cells. J Cell Commun Signal. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/32062833, https://doi.org/10.1007/s12079-020-00551-w
Riphagen JM, Ramakers I, Freeze WM, Pagen LHG, Hanseeuw BJ, Verbeek MM, . . . Jacobs HIL (2020) Linking APOE-epsilon4, blood-brain barrier dysfunction, and inflammation to Alzheimer's pathology. Neurobiol Aging 85:96–103. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31733942, https://doi.org/10.1016/j.neurobiolaging.2019.09.020
Rivera-Escalera F, Pinney JJ, Owlett L, Ahmed H, Thakar J, Olschowka JA, . . . O'Banion MK (2019) IL-1beta-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia. J Neuroinflammation 16(1):261. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31822279, https://doi.org/10.1186/s12974-019-1645-7
Saadane A, Petrov A, Mast N, El-Darzi N, Dao T, Alnemri A, . . . Pikuleva IA (2018) Mechanisms that minimize retinal impact of apolipoprotein E absence. J Lipid Res 59(12):2368–2382. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30333155, https://doi.org/10.1194/jlr.M090043
Samaha MM, Helal MG, El-Sherbiny M, Said E, Salem HA (2022) Indapamide Increases IRS1 Expression and Modifies Adiponectin/NLRP3/PPARγ Crosstalk in Type 2 Diabetic Rats. Antioxidants (Basel) 11(4). Retrieved from https://www.mdpi.com/2076-3921/11/4/691, https://mdpi-res.com/d_attachment/antioxidants/antioxidants-11-00691/article_deploy/antioxidants-11-00691.pdf?version=1648729392, https://doi.org/10.3390/antiox11040691
Sauer S (2015) Ligands for the nuclear peroxisome proliferator-activated receptor gamma. Trends Pharmacol Sci 36(10):688–704. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/26435213, https://doi.org/10.1016/j.tips.2015.06.010
Schafer I, Kaisler J, Scheller A, Kirchhoff F, Haghikia A, Faissner A (2019) Conditional deletion of LRP1 leads to progressive loss of recombined NG2-expressing oligodendrocyte precursor cells in a novel mouse model. Cells 8(12). Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31801252, https://doi.org/10.3390/cells8121550
Seok H, Lee M, Shin E, Yun MR, Lee YH, Moon JH, . . . Cha BS (2019) Low-dose pioglitazone can ameliorate learning and memory impairment in a mouse model of dementia by increasing LRP1 expression in the hippocampus. Sci Rep 9(1):4414. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30867485, https://doi.org/10.1038/s41598-019-40736-x
Sheedy FJ, Grebe A, Rayner KJ, Kalantari P, Ramkhelawon B, Carpenter SB, . . . Moore KJ (2013) CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation. Nat Immunol 14(8):812–820. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/23812099, https://doi.org/10.1038/ni.2639
Shibuya Y, Chang CC, Chang TY (2015) ACAT1/SOAT1 as a therapeutic target for Alzheimer’s disease. Future Med Chem 7(18):2451–2467. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/26669800, https://doi.org/10.4155/fmc.15.161
Shmuel-Galia L, Klug Y, Porat Z, Charni M, Zarmi B, Shai Y (2017) Intramembrane attenuation of the TLR4-TLR6 dimer impairs receptor assembly and reduces microglia-mediated neurodegeneration. J Biol Chem 292(32):13415–13427. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/28655763, https://doi.org/10.1074/jbc.M117.784983
Singh RK, Haka AS, Asmal A, Barbosa-Lorenzi VC, Grosheva I, Chin HF, . . . Maxfield FR (2020) TLR4 (Toll-Like Receptor 4)-Dependent signaling drives extracellular catabolism of LDL (Low-Density Lipoprotein) aggregates. Arterioscler Thromb Vasc Biol 40(1):86–102. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31597445, https://doi.org/10.1161/ATVBAHA.119.313200
Sokolova A, Hill MD, Rahimi F, Warden LA, Halliday GM, Shepherd CE (2009) Monocyte chemoattractant protein-1 plays a dominant role in the chronic inflammation observed in Alzheimer’s disease. Brain Pathol 19(3):392–398. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094842/pdf/BPA-19-392.pdf, https://doi.org/10.1111/j.1750-3639.2008.00188.x
Souza LC, Andrade MK, Azevedo EM, Ramos DC, Bail EL, Vital M (2022) Andrographolide attenuates short-term spatial and recognition memory impairment and neuroinflammation induced by a streptozotocin rat model of alzheimer’s disease. Neurotox Res 40(5):1440–1454. Retrieved from https://link.springer.com/article/10.1007/s12640-022-00569-5, https://doi.org/10.1007/s12640-022-00569-5
Stancu IC, Lodder C, Botella Lucena P, Vanherle S, Gutiérrez de Ravé M, Terwel D, . . . Dewachter I (2022) The NLRP3 inflammasome modulates tau pathology and neurodegeneration in a tauopathy model. Glia 70(6):1117–1132. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307007/pdf/GLIA-70-1117.pdf, https://doi.org/10.1002/glia.24160
Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, . . . Moore KJ (2010) CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol 11(2):155–161. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20037584, https://doi.org/10.1038/ni.1836
Storck SE, Hartz AMS, Bernard J, Wolf A, Kachlmeier A, Mahringer A, . . . Pietrzik CU (2018) The concerted amyloid-beta clearance of LRP1 and ABCB1/P-gp across the blood-brain barrier is linked by PICALM. Brain Behav Immun 73:21–33. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30041013, https://doi.org/10.1016/j.bbi.2018.07.017
Tachibana M, Holm ML, Liu CC, Shinohara M, Aikawa T, Oue H, . . . Kanekiyo T (2019) APOE4-mediated amyloid-beta pathology depends on its neuronal receptor LRP1. J Clin Invest 129(3):1272–1277. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30741718, https://doi.org/10.1172/JCI124853
Tang HB, Lu ZL, Wei XK, Zhong TZ, Zhong YZ, Ouyang LX, . . . Luo TR (2016). Viperin inhibits rabies virus replication via reduced cholesterol and sphingomyelin and is regulated upstream by TLR4. Sci Rep 6:30529. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/27456665, https://doi.org/10.1038/srep30529
Thakur S, Dhapola R, Sarma P, Medhi B, Reddy DH (2022) Neuroinflammation in alzheimer’s disease: current progress in molecular signaling and therapeutics. Inflammation. Retrieved from https://link.springer.com/article/10.1007/s10753-022-01721-1, https://doi.org/10.1007/s10753-022-01721-1
Tian M, Zhou F, Teng Z, Wang C, Zhang X, Wang Y, Li Y (2021) Curcumin ameliorates lipid metabolic disorder and cognitive dysfunction via the ABCA1 transmembrane transport system in APP/PS1 double transgenic mice. J Integr Neurosci 20(4):895–903. Retrieved from https://api.imrpress.com/sci/redirect/article/pdf?journal=JIN&volumeCode=20&issueCode=4&doi=10.31083/j.jin2004091, https://doi.org/10.31083/j.jin2004091
Viswakarma N, Jia Y, Bai L, Vluggens A, Borensztajn J, Xu J, Reddy JK (2010) Coactivators in PPAR-Regulated Gene Expression. PPAR Res 2010. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20814439, https://doi.org/10.1155/2010/250126
Wang N, Yvan-Charvet L, Lutjohann D, Mulder M, Vanmierlo T, Kim TW, Tall AR (2008) ATP-binding cassette transporters G1 and G4 mediate cholesterol and desmosterol efflux to HDL and regulate sterol accumulation in the brain. FASEB J 22(4):1073–1082. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18039927, https://doi.org/10.1096/fj.07-9944com
Wang X, Luo J, Li N, Liu L, Han X, Liu C, . . . Si S (2018a) E3317 promotes cholesterol efflux in macrophage cells via enhancing ABCA1 expression. Biochem Biophys Res Commun 504(1):68–74. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30173890, https://doi.org/10.1016/j.bbrc.2018.08.125
Wang Y, Chen Q, Tan Q, Feng Z, He Z, Tang J, . . . Chen Z (2018b) Simvastatin accelerates hematoma resolution after intracerebral hemorrhage in a PPARgamma-dependent manner. Neuropharmacology 128:244–254. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/29054366, https://doi.org/10.1016/j.neuropharm.2017.10.021
Wang ZF, Li J, Ma C, Huang C, Li ZQ (2019) Telmisartan ameliorates Abeta oligomer-induced inflammation via PPARgamma/PTEN pathway in BV2 microglial cells. Biochem Pharmacol: 113674. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31634455, https://doi.org/10.1016/j.bcp.2019.113674
Wei S, Zhang L, Bailu W, Zhao Y, Dong Q, Pan C, . . . Chen Y (2019) ALDH2 deficiency inhibits Ox-LDL induced foam cell formation via suppressing CD36 expression. Biochem Biophys Res Commun 512(1):41–48. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30853183, https://doi.org/10.1016/j.bbrc.2019.02.012
Weidner C, de Groot JC, Prasad A, Freiwald A, Quedenau C, Kliem M, . . . Sauer S (2012) Amorfrutins are potent antidiabetic dietary natural products. Proc Natl Acad Sci U S A 109(19):7257–7262. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22509006, https://doi.org/10.1073/pnas.1116971109
Wilson M (2011) Developmental and comparative immunology. Editorial. Dev Comp Immunol 35(9):884–885. https://doi.org/10.1016/j.dci.2011.06.007
Xie X, Zhou X, Chen W, Long L, Li W, Yang X, . . . Wang L (2015) L312, a novel PPARgamma ligand with potent anti-diabetic activity by selective regulation. Biochim Biophys Acta 1850(1):62–72. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25305559, https://doi.org/10.1016/j.bbagen.2014.09.027
Xie Z, Zhao J, Wang H, Jiang Y, Yang Q, Fu Y, . . . Zhang Z (2020) Magnolol alleviates Alzheimer's disease-like pathology in transgenic C. elegans by promoting microglia phagocytosis and the degradation of beta-amyloid through activation of PPAR-gamma. Biomed Pharmacother 124:109886. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/32000045, https://doi.org/10.1016/j.biopha.2020.109886
Xiong H, Callaghan D, Jones A, Walker DG, Lue LF, Beach TG, . . . Zhang W (2008) Cholesterol retention in Alzheimer's brain is responsible for high beta- and gamma-secretase activities and Abeta production. Neurobiol Dis 29(3):422–437. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18086530, https://doi.org/10.1016/j.nbd.2007.10.005
Xu GB, Yang LQ, Guan PP, Wang ZY, Wang P (2019a) Prostaglandin A1 inhibits the cognitive decline of APP/PS1 transgenic Mice via PPARgamma/ABCA1-dependent cholesterol efflux mechanisms. Neurotherapeutics 16(2):505–522. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30627958, https://doi.org/10.1007/s13311-018-00704-1
Xu GB, Yang LQ, Guan PP, Wang ZY, Wang P (2019b) Prostaglandin A1 inhibits the cognitive decline of APP/PS1 transgenic Mice via PPARγ/ABCA1-dependent cholesterol efflux mechanisms. Neurotherapeutics 16(2):505–522. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554490/pdf/13311_2018_Article_704.pdf, https://doi.org/10.1007/s13311-018-00704-1
Yamanaka M, Ishikawa T, Griep A, Axt D, Kummer MP, Heneka MT (2012) PPARgamma/RXRalpha-induced and CD36-mediated microglial amyloid-beta phagocytosis results in cognitive improvement in amyloid precursor protein/presenilin 1 mice. J Neurosci 32(48):17321–17331. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/23197723, https://doi.org/10.1523/JNEUROSCI.1569-12.2012
Ye K, Wu Y, Sun Y, Lin JA, Xu J (2016) TLR4 siRNA inhibits proliferation and invasion in colorectal cancer cells by downregulating ACAT1 expression. Life Sci 155:133–139. https://doi.org/10.1016/j.lfs.2016.05.012
Ye Z-J, Go G-W, Singh R, Liu W, Keramati AR, Mani A (2012) LRP6 Protein Regulates Low Density Lipoprotein (LDL) Receptor-mediated LDL uptake. J Biol Chem 287(2):1335–1344. https://doi.org/10.1074/jbc.M111.295287
Yoshizawa M, Aoyama T, Itoh T, Miyachi H (2022) Arylalkynyl amide-type peroxisome proliferator-activated receptor γ (PPARγ)-selective antagonists covalently bind to the PPARγ ligand binding domain with a unique binding mode. Bioorg Med Chem Lett 64:128676. https://doi.org/10.1016/j.bmcl.2022.128676
Zeng Q, Long Z, Feng M, Zhao Y, Luo S, Wang K, . . . He G (2019) Valproic acid stimulates hippocampal neurogenesis via activating the Wnt/beta-Catenin signaling pathway in the APP/PS1/Nestin-GFP triple transgenic mouse model of alzheimer's disease. Front Aging Neurosci 11:62. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30971911, https://doi.org/10.3389/fnagi.2019.00062
Zhang L, Zhou Z, Zhai W, Pang J, Mo Y, Yang G, . . . Hu Y (2019a) Safflower yellow attenuates learning and memory deficits in amyloid beta-induced Alzheimer's disease rats by inhibiting neuroglia cell activation and inflammatory signaling pathways. Metab Brain Dis 34(3):927–939. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30830599, https://doi.org/10.1007/s11011-019-00398-0
Zhang M, Qian C, Zheng ZG, Qian F, Wang Y, Thu PM, . . . Xu X (2018) Jujuboside A promotes Abeta clearance and ameliorates cognitive deficiency in Alzheimer's disease through activating Axl/HSP90/PPARgamma pathway. Theranostics 8(15):4262–4278. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30128052, https://doi.org/10.7150/thno.26164
Zhang XL, Zhao N, Xu B, Chen XH, Li TJ (2019b) Treadmill exercise inhibits amyloid-beta generation in the hippocampus of APP/PS1 transgenic mice by reducing cholesterol-mediated lipid raft formation. Neuroreport 30(7):498–503. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30882716, https://doi.org/10.1097/WNR.0000000000001230
Zhang Y, Wang C, Jia ZL, Ma RJ, Wang XF, Chen WY, Liu KC (2020) Isoniazid promotes the anti-inflammatory response in zebrafish associated with regulation of the PPARgamma/NF-kappaB/AP-1 pathway. Chem Biol Interact 316:108928. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/31857089, https://doi.org/10.1016/j.cbi.2019.108928
Zhao N, Liu CC, Qiao W, Bu G (2018) Apolipoprotein E, receptors, and modulation of alzheimer’s disease. Biol Psychiatry 83(4):347–357. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/28434655, https://doi.org/10.1016/j.biopsych.2017.03.003
Zhao X, Sun G, Zhang J, Strong R, Song W, Gonzales N, . . . Aronowski J (2007) Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages. Ann Neurol 61(4):352–362. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17457822, https://doi.org/10.1002/ana.21097
Zheng W, Qiu L, Wang R, Feng X, Han Y, Zhu Y, . . . Li Y (2015) Selective targeting of PPARgamma by the natural product chelerythrine with a unique binding mode and improved antidiabetic potency. Sci Rep 5:12222. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/26183621, https://doi.org/10.1038/srep12222
Zhou L, Choi HY, Li WP, Xu F, Herz J (2009) LRP1 controls cPLA2 phosphorylation, ABCA1 expression and cellular cholesterol export. PLoS One 4(8):e6853. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19718435, https://doi.org/10.1371/journal.pone.0006853
Zhu G, Zhang J, Yue L, Xiang G (2022) Preventive effect of salicin ether against type-2 diabetes mellitus through targeting PPARγ-regulated gene expression. Acta Biochim Pol 69(3):619–623. Retrieved from https://ojs.ptbioch.edu.pl/index.php/abp/article/download/5983/5288, https://doi.org/10.18388/abp.2020_5983
Funding
The work was supported by the Natural Science Foundation of Zhejiang Province (LQ20H280001), Traditional Chinese Medicine Science and Technology Program of Zhejiang Provence (2021ZQ022), Medical and Health Science and Technology Project of Zhejiang Province (2021KY129) and Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province (2019E10021).
Author information
Authors and Affiliations
Contributions
These authors contributed equally to this work.
Corresponding author
Ethics declarations
Ethics approval
Not applicable.
Consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no conflict of interest.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Gu, L., Ju, Y., Hu, M. et al. Research progress of PPARγ regulation of cholesterol and inflammation in Alzheimer's disease. Metab Brain Dis 38, 839–854 (2023). https://doi.org/10.1007/s11011-022-01139-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-022-01139-6