{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:06:40Z","timestamp":1784041600412,"version":"3.55.0"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":55,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"NRF","award":["\ufeffRS-2024-00357857"],"award-info":[{"award-number":["\ufeffRS-2024-00357857"]}]},{"name":"KDRC","award":["\ufeffRS-2024-00343370"],"award-info":[{"award-number":["\ufeffRS-2024-00343370"]}]},{"DOI":"10.13039\/501100003665","name":"NIPA","doi-asserted-by":"crossref","award":["\ufeffH0501-25-1001"],"award-info":[{"award-number":["\ufeffH0501-25-1001"]}],"id":[{"id":"10.13039\/501100003665","id-type":"DOI","asserted-by":"crossref"}]},{"name":"\ufeffWhanin Pharm Co., Ltd","award":["\ufeff20190058"],"award-info":[{"award-number":["\ufeff20190058"]}]},{"name":"KBRI funded by the Ministry of Science, ICT & Future Planning","award":["26-BR-02-04, 26-BR-05-01, and 26-BR-06-01"],"award-info":[{"award-number":["26-BR-02-04, 26-BR-05-01, and 26-BR-06-01"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2026-25492172"],"award-info":[{"award-number":["RS-2026-25492172"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"DOI":"10.1186\/s12974-026-03855-7","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T11:06:29Z","timestamp":1779275189000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The insulin receptor inhibitor BMS-754807 alleviates neuroinflammation and Alzheimer\u2019s disease pathologies across human cellular and mouse models"],"prefix":"10.1186","volume":"23","author":[{"given":"Hyun-ju","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaewoo","family":"Seok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sora","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seokjun","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Woo","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsoo","family":"Seo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyang-Sook","family":"Hoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"3855_CR1","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/S0896-6273(02)00794-8","volume":"35","author":"T Wyss-Coray","year":"2002","unstructured":"Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease\u2014a double-edged sword. Neuron. 2002;35:419\u201332.","journal-title":"Neuron"},{"key":"3855_CR2","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/S0074-7742(07)82012-5","volume-title":"Neuroinflammation in neuronal death and repair","author":"J Rogers","year":"2007","unstructured":"Rogers J, Mastroeni D, Leonard B, Joyce J, Grover A. Neuroinflammation in Alzheimer\u2019s Disease and Parkinson\u2019s Disease: are microglia pathogenic in either disorder? In: Neuroinflammation in neuronal death and repair. 2007. p. 235\u201346."},{"key":"3855_CR3","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s40035-020-00221-2","volume":"9","author":"HS Kwon","year":"2020","unstructured":"Kwon HS, Koh S-H. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Transl Neurodegener. 2020;9:42.","journal-title":"Transl Neurodegener"},{"key":"3855_CR4","doi-asserted-by":"publisher","first-page":"258","DOI":"10.3389\/fnmol.2019.00258","volume":"12","author":"TH Palpagama","year":"2019","unstructured":"Palpagama TH, Waldvogel HJ, Faull RLM, Kwakowsky A. The role of microglia and astrocytes in Huntington\u2019s Disease. Front Mol Neurosci. 2019;12:258.","journal-title":"Front Mol Neurosci"},{"key":"3855_CR5","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1186\/s12974-019-1561-x","volume":"16","author":"KY Ryu","year":"2019","unstructured":"Ryu KY, Lee HJ, Woo H, Kang RJ, Han KM, Park H, et al. Dasatinib regulates LPS-induced microglial and astrocytic neuroinflammatory responses by inhibiting AKT\/STAT3 signaling. J Neuroinflammation. 2019;16:190.","journal-title":"J Neuroinflammation"},{"issue":"Suppl 2","key":"3855_CR6","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/jnc.13607","volume":"139","author":"DJ DiSabato","year":"2016","unstructured":"DiSabato DJ, Quan N, Godbout JP. Neuroinflammation: the devil is in the details. J Neurochem. 2016;139(Suppl 2):136\u201353.","journal-title":"J Neurochem"},{"key":"3855_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.54117\/sjmams.v1i1.1","volume":"1","author":"B Adetuyi","year":"2021","unstructured":"Adetuyi B, Toloyai P-E, Ojugbeli E, Oyebanjo O, Adetuyi O, Uche C, et al. Neurorestorative roles of microgliosis and astrogliosis in neuroinflammation and neurodegeneration. Scicom J Med Appl Med Sci. 2021;1:1\u20135.","journal-title":"Scicom J Med Appl Med Sci"},{"key":"3855_CR8","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006338","volume":"2","author":"L Mucke","year":"2012","unstructured":"Mucke L, Selkoe DJ. Neurotoxicity of amyloid beta-protein: synaptic and network dysfunction. Cold Spring Harb Perspect Med. 2012;2:a006338.","journal-title":"Cold Spring Harb Perspect Med"},{"key":"3855_CR9","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1038\/aps.2017.28","volume":"38","author":"GF Chen","year":"2017","unstructured":"Chen GF, Xu TH, Yan Y, Zhou YR, Jiang Y, Melcher K, et al. Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol Sin. 2017;38:1205\u201335.","journal-title":"Acta Pharmacol Sin"},{"key":"3855_CR10","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1081938","volume":"17","author":"MO Iliyasu","year":"2023","unstructured":"Iliyasu MO, Musa SA, Oladele SB, Iliya AI. Amyloid-beta aggregation implicates multiple pathways in Alzheimer\u2019s disease: understanding the mechanisms. Front Neurosci. 2023;17:1081938.","journal-title":"Front Neurosci"},{"key":"3855_CR11","doi-asserted-by":"crossref","unstructured":"Tamagno E, Guglielmotto M, Vasciaveo V, Tabaton M. Oxidative stress and beta amyloid in Alzheimer's disease. Which comes first: the chicken or the egg? Antioxidants (Basel). 2021;10(9):1479.","DOI":"10.3390\/antiox10091479"},{"key":"3855_CR12","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.redox.2017.10.014","volume":"14","author":"C Cheignon","year":"2018","unstructured":"Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer\u2019s disease. Redox Biol. 2018;14:450\u201364.","journal-title":"Redox Biol"},{"key":"3855_CR13","doi-asserted-by":"publisher","first-page":"2944","DOI":"10.1021\/acschemneuro.3c00486","volume":"14","author":"RG Roy","year":"2023","unstructured":"Roy RG, Mandal PK, Maroon JC. Oxidative stress occurs prior to amyloid Abeta plaque formation and tau phosphorylation in Alzheimer\u2019s Disease: role of glutathione and metal ions. ACS Chem Neurosci. 2023;14:2944\u201354.","journal-title":"ACS Chem Neurosci"},{"key":"3855_CR14","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1134\/S002689332104004X","volume":"55","author":"DG Garbuz","year":"2021","unstructured":"Garbuz DG, Zatsepina OG, Evgen\u2019ev MB. [Beta Amyloid, Tau Protein, and neuroinflammation: an attempt to integrate different hypotheses of Alzheimer\u2019s disease pathogenesis]. Mol Biol (Mosk). 2021;55:734\u201347.","journal-title":"Mol Biol (Mosk)"},{"key":"3855_CR15","doi-asserted-by":"publisher","first-page":"172","DOI":"10.3389\/fncel.2018.00172","volume":"12","author":"JR Perea","year":"2018","unstructured":"Perea JR, Llorens-Martin M, Avila J, Bolos M. The role of microglia in the spread of Tau: relevance for tauopathies. Front Cell Neurosci. 2018;12:172.","journal-title":"Front Cell Neurosci"},{"key":"3855_CR16","doi-asserted-by":"crossref","unstructured":"Herrero-Labrador R, Fernandez-Irigoyen J, Vecino R, Gonz\u00e1lez-Arias C, Ausin K, Crespo I, Fern\u00e1ndez Acosta FJ, Nieto-Est\u00e9vez V, Rom\u00e1n MJ, Perea G, Torres-Aleman I, Santamaria E, Vicario C. Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior. Life Sci Alliance. 2023;6(10):e202201691.","DOI":"10.26508\/lsa.202201691"},{"key":"3855_CR17","doi-asserted-by":"publisher","first-page":"365","DOI":"10.3389\/fnagi.2017.00365","volume":"9","author":"JL Labandeira-Garcia","year":"2017","unstructured":"Labandeira-Garcia JL, Costa-Besada MA, Labandeira CM, Villar-Cheda B, Rodriguez-Perez AI. Insulin-Like Growth Factor-1 and neuroinflammation. Front Aging Neurosci. 2017;9:365.","journal-title":"Front Aging Neurosci"},{"key":"3855_CR18","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s40478-023-01535-8","volume":"11","author":"DC Ivan","year":"2023","unstructured":"Ivan DC, Berve KC, Walthert S, Monaco G, Borst K, Bouillet E, et al. Insulin-like growth factor-1 receptor controls the function of CNS-resident macrophages and their contribution to neuroinflammation. Acta Neuropathol Commun. 2023;11:35.","journal-title":"Acta Neuropathol Commun"},{"key":"3855_CR19","doi-asserted-by":"publisher","first-page":"2887","DOI":"10.2147\/DDDT.S171638","volume":"12","author":"J Li","year":"2018","unstructured":"Li J, Dong R, Yu J, Yi S, Da J, Yu F, et al. Inhibitor of IGF1 receptor alleviates the inflammation process in the diabetic kidney mouse model without activating SOCS2. Drug Des Devel Ther. 2018;12:2887\u201396.","journal-title":"Drug Des Devel Ther"},{"key":"3855_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2020.111053","volume":"519","author":"LJ Yuan","year":"2021","unstructured":"Yuan LJ, Zhang M, Chen S, Chen WF. Anti-inflammatory effect of IGF-1 is mediated by IGF-1R cross talk with GPER in MPTP\/MPP(+)-induced astrocyte activation. Mol Cell Endocrinol. 2021;519:111053.","journal-title":"Mol Cell Endocrinol"},{"key":"3855_CR21","doi-asserted-by":"publisher","first-page":"2314","DOI":"10.1158\/1078-0432.CCR-10-1903","volume":"17","author":"BC Litzenburger","year":"2011","unstructured":"Litzenburger BC, Creighton CJ, Tsimelzon A, Chan BT, Hilsenbeck SG, Wang T, et al. High IGF-IR activity in triple-negative breast cancer cell lines and tumorgrafts correlates with sensitivity to anti-IGF-IR therapy. Clin Cancer Res. 2011;17:2314\u201327.","journal-title":"Clin Cancer Res"},{"key":"3855_CR22","doi-asserted-by":"publisher","first-page":"E1267","DOI":"10.1073\/pnas.1105034109","volume":"109","author":"A Bielen","year":"2012","unstructured":"Bielen A, Box G, Perryman L, Bjerke L, Popov S, Jamin Y, et al. Dependence of Wilms tumor cells on signaling through insulin-like growth factor 1 in an orthotopic xenograft model targetable by specific receptor inhibition. Proc Natl Acad Sci U S A. 2012;109:E1267\u201376.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3855_CR23","doi-asserted-by":"publisher","first-page":"3341","DOI":"10.1158\/1535-7163.MCT-09-0499","volume":"8","author":"JM Carboni","year":"2009","unstructured":"Carboni JM, Wittman M, Yang Z, Lee F, Greer A, Hurlburt W, et al. BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R\/IR. Mol Cancer Ther. 2009;8:3341\u20139.","journal-title":"Mol Cancer Ther"},{"key":"3855_CR24","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/s43856-025-00925-4","volume":"5","author":"AG Almer","year":"2025","unstructured":"Almer AG, Rasmussen SV, Kats D, Svalina MN, Cole BL, Khani M, et al. Computational and biological modeling of IGF1R inhibition for multifocal medulloblastoma. Commun Med (Lond). 2025;5:206.","journal-title":"Commun Med (Lond)"},{"key":"3855_CR25","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1016\/j.bmcl.2016.12.086","volume":"27","author":"J Prabhakaran","year":"2017","unstructured":"Prabhakaran J, Dewey SL, McClure R, Simpson NR, Tantawy MN, Mann JJ, et al. In vivo evaluation of IGF1R\/IR PET ligand [(18)F]BMS-754807 in rodents. Bioorg Med Chem Lett. 2017;27:941\u20133.","journal-title":"Bioorg Med Chem Lett"},{"key":"3855_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910637","author":"J Kim","year":"2021","unstructured":"Kim J, Lee HJ, Park SK, Park JH, Jeong HR, Lee S, et al. Donepezil regulates LPS and Abeta-stimulated neuroinflammation through MAPK\/NLRP3 inflammasome\/STAT3 signaling. Int J Mol Sci. 2021. https:\/\/doi.org\/10.3390\/ijms221910637.","journal-title":"Int J Mol Sci"},{"key":"3855_CR27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.903309","volume":"13","author":"J Kim","year":"2022","unstructured":"Kim J, Kim SJ, Jeong HR, Park JH, Moon M, Hoe HS. Inhibiting EGFR\/HER-2 ameliorates neuroinflammatory responses and the early stage of tau pathology through DYRK1A. Front Immunol. 2022;13:903309.","journal-title":"Front Immunol"},{"key":"3855_CR28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1150940","volume":"14","author":"JH Park","year":"2023","unstructured":"Park JH, Hwang JW, Lee HJ, Jang GM, Jeong YJ, Cho J, et al. Lomerizine inhibits LPS-mediated neuroinflammation and tau hyperphosphorylation by modulating NLRP3, DYRK1A, and GSK3alpha\/beta. Front Immunol. 2023;14:1150940.","journal-title":"Front Immunol"},{"key":"3855_CR29","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1186\/s12974-022-02549-0","volume":"19","author":"J Kim","year":"2022","unstructured":"Kim J, Lee HJ, Park JH, Cha BY, Hoe HS. Nilotinib modulates LPS-induced cognitive impairment and neuroinflammatory responses by regulating P38\/STAT3 signaling. J Neuroinflammation. 2022;19:187.","journal-title":"J Neuroinflammation"},{"key":"3855_CR30","doi-asserted-by":"publisher","first-page":"755","DOI":"10.3233\/JAD-210523","volume":"85","author":"A Sil","year":"2022","unstructured":"Sil A, Erfani A, Lamb N, Copland R, Riedel G, Platt B. Sex differences in behavior and molecular pathology in the 5XFAD model. J Alzheimers Dis. 2022;85:755\u201378.","journal-title":"J Alzheimers Dis"},{"key":"3855_CR31","doi-asserted-by":"publisher","DOI":"10.1186\/cc11670","volume":"16","author":"C Cao","year":"2012","unstructured":"Cao C, Yu X, Liao Z, Zhu N, Huo H, Wang M, et al. Hypertonic saline reduces lipopolysaccharide-induced mouse brain edema through inhibiting aquaporin 4 expression. Crit Care. 2012;16:R186.","journal-title":"Crit Care"},{"key":"3855_CR32","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-023-00810-7","volume":"24","author":"DH Kang","year":"2023","unstructured":"Kang DH, Ahn S, Chae JW, Song JS. Differential effects of two phosphodiesterase 4 inhibitors against lipopolysaccharide-induced neuroinflammation in mice. BMC Neurosci. 2023;24:39.","journal-title":"BMC Neurosci"},{"key":"3855_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.106725","volume":"190","author":"HJ Lee","year":"2023","unstructured":"Lee HJ, Hoe HS. Inhibition of CDK4\/6 regulates AD pathology, neuroinflammation and cognitive function through DYRK1A\/STAT3 signaling. Pharmacol Res. 2023;190:106725.","journal-title":"Pharmacol Res"},{"key":"3855_CR34","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1572604","volume":"16","author":"HJ Lee","year":"2025","unstructured":"Lee HJ, Kim SH, Jung TM, Kim YJ, Gu CH, Jeong YJ, et al. Erdafitinib diminishes LPS-mediated neuroinflammatory responses through NLRP3 in wild-type mice. Front Pharmacol. 2025;16:1572604.","journal-title":"Front Pharmacol"},{"key":"3855_CR35","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1016\/j.celrep.2019.01.023","volume":"26","author":"K Meyer","year":"2019","unstructured":"Meyer K, Feldman HM, Lu T, Drake D, Lim ET, Ling KH, et al. REST and neural gene network dysregulation in iPSC models of Alzheimer\u2019s disease. Cell Rep. 2019;26:1112-1127 e9.","journal-title":"Cell Rep"},{"key":"3855_CR36","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s12640-020-00197-x","volume":"38","author":"C-I Yu","year":"2020","unstructured":"Yu C-I, Cheng C-I, Kang Y-F, Chang P-C, Lin I-P, Kuo Y-H, et al. Hispidulin inhibits neuroinflammation in Lipopolysaccharide-activated BV2 microglia and attenuates the activation of Akt, NF-\u03baB, and STAT3 pathway. Neurotox Res. 2020;38:163\u201374.","journal-title":"Neurotox Res"},{"key":"3855_CR37","doi-asserted-by":"publisher","first-page":"7218","DOI":"10.1523\/JNEUROSCI.2574-18.2019","volume":"39","author":"L Passamonti","year":"2019","unstructured":"Passamonti L, Tsvetanov KA, Jones PS, Bevan-Jones WR, Arnold R, Borchert RJ, et al. Neuroinflammation and functional connectivity in Alzheimer\u2019s Disease: interactive influences on cognitive performance. J Neurosci. 2019;39:7218\u201326.","journal-title":"J Neurosci"},{"key":"3855_CR38","doi-asserted-by":"publisher","first-page":"2012","DOI":"10.1093\/brain\/awx132","volume":"140","author":"C George","year":"2017","unstructured":"George C, Gontier G, Lacube P, Francois JC, Holzenberger M, Aid S. The Alzheimer\u2019s disease transcriptome mimics the neuroprotective signature of IGF-1 receptor-deficient neurons. Brain. 2017;140:2012\u201327.","journal-title":"Brain"},{"key":"3855_CR39","doi-asserted-by":"crossref","unstructured":"Wu D, Dong S, Zhou W. Insulin\u2011like growth factor in cancer: new perspectives (Review). Mol Med Rep. 2025;32(2):209.","DOI":"10.3892\/mmr.2025.13574"},{"key":"3855_CR40","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.pnpbp.2015.06.008","volume":"64","author":"YK Kim","year":"2016","unstructured":"Kim YK, Na KS, Myint AM, Leonard BE. The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2016;64:277\u201384.","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"3855_CR41","doi-asserted-by":"crossref","unstructured":"He Y, Lee SMY. Brain ventricular microinjections of lipopolysaccharide into larval zebrafish to assess neuroinflammation and neurotoxicity. J Vis Exp. 2022;(186):e64313.","DOI":"10.3791\/64313-v"},{"key":"3855_CR42","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","volume":"14","author":"MT Heneka","year":"2015","unstructured":"Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer\u2019s disease. Lancet Neurol. 2015;14:388\u2013405.","journal-title":"Lancet Neurol"},{"key":"3855_CR43","doi-asserted-by":"publisher","first-page":"2158","DOI":"10.1016\/j.bbadis.2017.06.002","volume":"1863","author":"MC Erlandsson","year":"2017","unstructured":"Erlandsson MC, Silfversward ST, Nadali M, Turkkila M, Svensson MND, Jonsson IM, et al. IGF-1R signalling contributes to IL-6 production and T cell dependent inflammation in rheumatoid arthritis. Biochimica et Biophysica Acta (BBA). 2017;1863:2158\u201370.","journal-title":"Biochimica et Biophysica Acta (BBA)"},{"key":"3855_CR44","doi-asserted-by":"publisher","first-page":"E12063","DOI":"10.1073\/pnas.1810553115","volume":"115","author":"KME Andersson","year":"2018","unstructured":"Andersson KME, Wasen C, Juzokaite L, Leifsdottir L, Erlandsson MC, Silfversward ST, et al. Inflammation in the hippocampus affects IGF1 receptor signaling and contributes to neurological sequelae in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2018;115:E12063\u201372.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3855_CR45","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1016\/j.cell.2009.11.014","volume":"139","author":"E Cohen","year":"2009","unstructured":"Cohen E, Paulsson JF, Blinder P, Burstyn-Cohen T, Du D, Estepa G, et al. Reduced IGF-1 signaling delays age-associated proteotoxicity in mice. Cell. 2009;139:1157\u201369.","journal-title":"Cell"},{"key":"3855_CR46","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00067","volume":"13","author":"V Fuentes-Santamaria","year":"2019","unstructured":"Fuentes-Santamaria V, Alvarado JC, Rodriguez-de la Rosa L, Juiz JM, Varela-Nieto I. Neuroglial involvement in abnormal glutamate transport in the cochlear nuclei of the Igf1 (-\/-) mouse. Front Cell Neurosci. 2019;13:67.","journal-title":"Front Cell Neurosci"},{"key":"3855_CR47","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1038\/nm.4397","volume":"23","author":"MW Salter","year":"2017","unstructured":"Salter MW, Stevens B. Microglia emerge as central players in brain disease. Nat Med. 2017;23:1018\u201327.","journal-title":"Nat Med"},{"key":"3855_CR48","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/j.it.2020.07.004","volume":"41","author":"MV Sofroniew","year":"2020","unstructured":"Sofroniew MV. Astrocyte reactivity: subtypes, states, and functions in CNS innate immunity. Trends Immunol. 2020;41:758\u201370.","journal-title":"Trends Immunol"},{"key":"3855_CR49","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.neurobiolaging.2021.09.006","volume":"109","author":"H Patel","year":"2022","unstructured":"Patel H, Martinez P, Perkins A, Taylor X, Jury N, McKinzie D, et al. Pathological tau and reactive astrogliosis are associated with distinct functional deficits in a mouse model of tauopathy. Neurobiol Aging. 2022;109:52\u201363.","journal-title":"Neurobiol Aging"},{"key":"3855_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-04561-4","volume":"7","author":"S Pineiro-Hermida","year":"2017","unstructured":"Pineiro-Hermida S, Lopez IP, Alfaro-Arnedo E, Torrens R, Iniguez M, Alvarez-Erviti L, et al. IGF1R deficiency attenuates acute inflammatory response in a bleomycin-induced lung injury mouse model. Sci Rep. 2017;7:4290.","journal-title":"Sci Rep"},{"key":"3855_CR51","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-48","volume":"11","author":"D Doens","year":"2014","unstructured":"Doens D, Fernandez PL. Microglia receptors and their implications in the response to amyloid beta for Alzheimer\u2019s disease pathogenesis. J Neuroinflammation. 2014;11:48.","journal-title":"J Neuroinflammation"},{"key":"3855_CR52","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13024-018-0254-8","volume":"13","author":"S Rangaraju","year":"2018","unstructured":"Rangaraju S, Dammer EB, Raza SA, Rathakrishnan P, Xiao H, Gao T, et al. Identification and therapeutic modulation of a pro-inflammatory subset of disease-associated-microglia in Alzheimer\u2019s disease. Mol Neurodegener. 2018;13:24.","journal-title":"Mol Neurodegener"},{"key":"3855_CR53","doi-asserted-by":"publisher","first-page":"T69","DOI":"10.1530\/JME-17-0311","volume":"61","author":"F Hakuno","year":"2018","unstructured":"Hakuno F, Takahashi SI. IGF1 receptor signaling pathways. J Mol Endocrinol. 2018;61:T69\u201386.","journal-title":"J Mol Endocrinol"},{"key":"3855_CR54","doi-asserted-by":"publisher","DOI":"10.1186\/s42826-019-0018-9","volume":"35","author":"JB Kang","year":"2019","unstructured":"Kang JB, Park DJ, Shah MA, Kim MO, Koh PO. Lipopolysaccharide induces neuroglia activation and NF-kappaB activation in cerebral cortex of adult mice. Lab Anim Res. 2019;35:19.","journal-title":"Lab Anim Res"},{"key":"3855_CR55","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1308-0","volume":"15","author":"HY Nam","year":"2018","unstructured":"Nam HY, Nam JH, Yoon G, Lee J-Y, Nam Y, Kang H-J, et al. Ibrutinib suppresses LPS-induced neuroinflammatory responses in BV2 microglial cells and wild-type mice. J Neuroinflammation. 2018;15:271.","journal-title":"J Neuroinflammation"},{"key":"3855_CR56","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1203\/01.pdr.0000238257.15502.f4","volume":"60","author":"A Chetty","year":"2006","unstructured":"Chetty A, Cao G-J, Nielsen HC. Insulin-like growth factor-I signaling mechanisms, type I collagen and alpha smooth muscle actin in human fetal lung fibroblasts. Pediatr Res. 2006;60:389\u201394.","journal-title":"Pediatr Res"},{"key":"3855_CR57","doi-asserted-by":"publisher","first-page":"8384","DOI":"10.1074\/jbc.M112.341586","volume":"287","author":"S Basu","year":"2012","unstructured":"Basu S, Rajakaruna S, Menko AS. Insulin-like growth factor receptor-1 and nuclear factor kappaB are crucial survival signals that regulate caspase-3-mediated lens epithelial cell differentiation initiation. J Biol Chem. 2012;287:8384\u201397.","journal-title":"J Biol Chem"},{"key":"3855_CR58","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcp.2020.101583","volume":"52","author":"C Wang","year":"2020","unstructured":"Wang C, An Y, Wang Y, Shen K, Wang X, Luan W, et al. Insulin-like growth factor-I activates NFkappaB and NLRP3 inflammatory signalling via ROS in cancer cells. Mol Cell Probes. 2020;52:101583.","journal-title":"Mol Cell Probes"},{"key":"3855_CR59","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.2147\/JIR.S339483","volume":"15","author":"W Tang","year":"2022","unstructured":"Tang W, Lv Q, Huang X, Li Y, Zou J, Zheng J, et al. MiR-143 targets IGF-1R to suppress autoimmunity in thyroid-associated ophthalmopathy. J Inflamm Res. 2022;15:1543\u201354.","journal-title":"J Inflamm Res"},{"key":"3855_CR60","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046364","volume":"7","author":"H Yang","year":"2012","unstructured":"Yang H, Zhang W, Pan H, Feldser HG, Lainez E, Miller C, et al. SIRT1 activators suppress inflammatory responses through promotion of p65 deacetylation and inhibition of NF-kappaB activity. PLoS ONE. 2012;7:e46364.","journal-title":"PLoS ONE"},{"key":"3855_CR61","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.bbadis.2017.12.027","volume":"1864","author":"P Liu","year":"2018","unstructured":"Liu P, Huang G, Wei T, Gao J, Huang C, Sun M, et al. Sirtuin 3-induced macrophage autophagy in regulating NLRP3 inflammasome activation. Biochim Biophys Acta Mol Basis Dis. 2018;1864:764\u201377.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"3855_CR62","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1523\/JNEUROSCI.4469-04.2005","volume":"25","author":"S Rosi","year":"2005","unstructured":"Rosi S, Ramirez-Amaya V, Vazdarjanova A, Worley PF, Barnes CA, Wenk GL. Neuroinflammation alters the hippocampal pattern of behaviorally induced Arc expression. J Neurosci. 2005;25:723\u201331.","journal-title":"J Neurosci"},{"key":"3855_CR63","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/nature11729","volume":"493","author":"MT Heneka","year":"2013","unstructured":"Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, et al. NLRP3 is activated in Alzheimer\u2019s disease and contributes to pathology in APP\/PS1 mice. Nature. 2013;493:674\u20138.","journal-title":"Nature"},{"key":"3855_CR64","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1093\/brain\/awv379","volume":"139","author":"A Olmos-Alonso","year":"2016","unstructured":"Olmos-Alonso A, Schetters ST, Sri S, Askew K, Mancuso R, Vargas-Caballero M, et al. Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer\u2019s-like pathology. Brain. 2016;139:891\u2013907.","journal-title":"Brain"},{"key":"3855_CR65","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1038\/nm1202-793","volume":"8","author":"E Carro","year":"2002","unstructured":"Carro E, Trejo JL, Gomez-Isla T, LeRoith D, Torres-Aleman I. Serum insulin-like growth factor I regulates brain amyloid-beta levels. Nat Med. 2002;8:1390\u20137.","journal-title":"Nat Med"},{"key":"3855_CR66","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2023.137189","volume":"808","author":"M Wang","year":"2023","unstructured":"Wang M, Zhao H, Zhang Z, Zhao Z, Wu H. Down-regulating insulin-like growth factor-1 receptor reduces amyloid-beta deposition in mice cortex induced by chronic sleep restriction. Neurosci Lett. 2023;808:137189.","journal-title":"Neurosci Lett"},{"key":"3855_CR67","doi-asserted-by":"publisher","first-page":"4418","DOI":"10.1073\/pnas.1916895117","volume":"117","author":"T Sen","year":"2020","unstructured":"Sen T, Saha P, Jiang T, Sen N. Sulfhydration of AKT triggers Tau-phosphorylation by activating glycogen synthase kinase 3beta in Alzheimer\u2019s disease. Proc Natl Acad Sci U S A. 2020;117:4418\u201327.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3855_CR68","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.116065","volume":"265","author":"Z Cheng","year":"2024","unstructured":"Cheng Z, Han T, Yao J, Wang K, Dong X, Yu F, et al. Targeting glycogen synthase kinase-3beta for Alzheimer\u2019s disease: recent advances and future prospects. Eur J Med Chem. 2024;265:116065.","journal-title":"Eur J Med Chem"},{"key":"3855_CR69","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0235543","volume":"15","author":"J Neddens","year":"2020","unstructured":"Neddens J, Daurer M, Flunkert S, Beutl K, Loeffler T, Walker L, et al. Correlation of pyroglutamate amyloid beta and ptau Ser202\/Thr205 levels in Alzheimer\u2019s disease and related murine models. PLoS ONE. 2020;15:e0235543.","journal-title":"PLoS ONE"},{"key":"3855_CR70","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81304-6","volume":"11","author":"J Shin","year":"2021","unstructured":"Shin J, Park S, Lee H, Kim Y. Thioflavin-positive tau aggregates complicating quantification of amyloid plaques in the brain of 5XFAD transgenic mouse model. Sci Rep. 2021;11:1617.","journal-title":"Sci Rep"},{"key":"3855_CR71","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2501527122","volume":"122","author":"W Chen","year":"2025","unstructured":"Chen W, Liu X, Munoz VR, Kahn CR. Loss of insulin signaling in microglia impairs cellular uptake of Abeta and neuroinflammatory response exacerbating AD-like neuropathology. Proc Natl Acad Sci U S A. 2025;122:e2501527122.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3855_CR72","doi-asserted-by":"publisher","first-page":"28068","DOI":"10.1074\/jbc.M113.505032","volume":"288","author":"T Anastassiadis","year":"2013","unstructured":"Anastassiadis T, Duong-Ly KC, Deacon SW, Lafontant A, Ma H, Devarajan K, et al. A highly selective dual insulin receptor (IR)\/insulin-like growth factor 1 receptor (IGF-1R) inhibitor derived from an extracellular signal-regulated kinase (ERK) inhibitor. J Biol Chem. 2013;288:28068\u201377.","journal-title":"J Biol Chem"},{"key":"3855_CR73","doi-asserted-by":"publisher","first-page":"3848","DOI":"10.1016\/j.febslet.2008.10.026","volume":"582","author":"F Hernandez","year":"2008","unstructured":"Hernandez F, Avila J. The role of glycogen synthase kinase 3 in the early stages of Alzheimers\u2019 disease. FEBS Lett. 2008;582:3848\u201354.","journal-title":"FEBS Lett"},{"key":"3855_CR74","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/nrn3505","volume":"14","author":"B Lu","year":"2013","unstructured":"Lu B, Nagappan G, Guan X, Nathan PJ, Wren P. BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nat Rev Neurosci. 2013;14:401\u201316.","journal-title":"Nat Rev Neurosci"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-026-03855-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-026-03855-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-026-03855-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T14:36:40Z","timestamp":1784039800000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12974-026-03855-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":74,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3855"],"URL":"https:\/\/doi.org\/10.1186\/s12974-026-03855-7","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"assertion":[{"value":"17 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experiments were approved by the institutional biosafety committee (IBC) of the Korea Brain Research Institute (KBRI) and Yonsei University and performed in accordance with approved animal protocols of KBRI (KBRI, approval no. IACUC-19\u201400049 and IACUC-24\u201400004; Yonsei University, approval no. IBC-D-202509\u2014447\u201491). The institutional review board (IRB) of Yonsei University approved the use of hiPSCs (approval no. 7001988\u2014202505-BR-2742\u201401E).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"245"}}