{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:10:54Z","timestamp":1793211054733,"version":"4.5.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A2B5B01070108"],"award-info":[{"award-number":["2019R1A2B5B01070108"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1F1A1057865"],"award-info":[{"award-number":["2021R1F1A1057865"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"KBRI basic research program","award":["22-BR-02-03"],"award-info":[{"award-number":["22-BR-02-03"]}]},{"name":"KBRI basic research program","award":["22-BR-03-05"],"award-info":[{"award-number":["22-BR-03-05"]}]},{"name":"KBRI basic research program","award":["22-BR-04-01"],"award-info":[{"award-number":["22-BR-04-01"]}]},{"name":"KBRI basic research program","award":["22-BR-02-12"],"award-info":[{"award-number":["22-BR-02-12"]}]},{"name":"Whanin Pharm Co., Ltd.","award":["20190058"],"award-info":[{"award-number":["20190058"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>In chronic myelogenous leukemia, reciprocal translocation between chromosome 9 and chromosome 22 generates a chimeric protein, Bcr-Abl, that leads to hyperactivity of tyrosine kinase-linked signaling transduction. The therapeutic agent nilotinib inhibits Bcr-Abl\/DDR1 and can cross the blood\u2013brain barrier, but its potential impact on neuroinflammatory responses and cognitive function has not been studied in detail.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The effects of nilotinib in vitro and in vivo were assessed by a combination of RT-PCR, real-time PCR, western blotting, ELISA, immunostaining, and\/or subcellular fractionation. In the in vitro experiments, the effects of 200\u00a0ng\/mL LPS or PBS on BV2 microglial cells, primary microglia or primary astrocytes pre- or post-treated with 5\u00a0\u00b5M nilotinib or vehicle were evaluated. The in vivo experiments involved wild-type mice administered a 7-day course of daily injections with 20\u00a0mg\/kg nilotinib (i.p.) or vehicle before injection with 10\u00a0mg\/kg LPS (i.p.) or PBS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In BV2 microglial cells, pre- and post-treatment with nilotinib altered LPS-induced proinflammatory\/anti-inflammatory cytokine mRNA levels by suppressing AKT\/P38\/SOD2 signaling. Nilotinib treatment also significantly downregulated LPS-stimulated proinflammatory cytokine levels in primary microglia and primary astrocytes by altering P38\/STAT3 signaling. Experiments in wild-type mice showed that nilotinib administration affected LPS-mediated microglial\/astroglial activation in a brain region-specific manner in vivo. In addition, nilotinib significantly reduced proinflammatory cytokine IL-1\u03b2, IL-6 and COX-2 levels and P38\/STAT3 signaling in the brain in LPS-treated wild-type mice. Importantly, nilotinib treatment rescued LPS-mediated spatial working memory impairment and cortical dendritic spine number in wild-type mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our results indicate that nilotinib can modulate neuroinflammatory responses and cognitive function in LPS-stimulated wild-type mice.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-022-02549-0","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T13:05:14Z","timestamp":1657890314000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Nilotinib modulates LPS-induced cognitive impairment and neuroinflammatory responses by regulating P38\/STAT3 signaling"],"prefix":"10.1186","volume":"19","author":[{"given":"Jieun","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-ju","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Hee","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung-Yoon","family":"Cha","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":[[2022,7,15]]},"reference":[{"issue":"2","key":"2549_CR1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.470","volume":"7","author":"FL Pagan","year":"2019","unstructured":"Pagan FL, Hebron ML, Wilmarth B, Torres-Yaghi Y, Lawler A, Mundel EE, Yusuf N, Starr NJ, Arellano J, Howard HH, et al. Pharmacokinetics and pharmacodynamics of a single dose nilotinib in individuals with Parkinson\u2019s disease. Pharmacol Res Perspect. 2019;7(2): e00470.","journal-title":"Pharmacol Res Perspect"},{"key":"2549_CR2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/637059","volume":"2014","author":"M Reinwald","year":"2014","unstructured":"Reinwald M, Schleyer E, Kiewe P, Blau IW, Burmeister T, Pursche S, Neumann M, Notter M, Thiel E, Hofmann WK, et al. Efficacy and pharmacologic data of second-generation tyrosine kinase inhibitor nilotinib in BCR-ABL-positive leukemia patients with central nervous system relapse after allogeneic stem cell transplantation. Biomed Res Int. 2014;2014: 637059.","journal-title":"Biomed Res Int"},{"issue":"1\u20132","key":"2549_CR3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.bbapap.2005.07.040","volume":"1754","author":"PW Manley","year":"2005","unstructured":"Manley PW, Cowan-Jacob SW, Mestan J. Advances in the structural biology, design and clinical development of Bcr-Abl kinase inhibitors for the treatment of chronic myeloid leukaemia. Biochim Biophys Acta. 2005;1754(1\u20132):3\u201313.","journal-title":"Biochim Biophys Acta"},{"key":"2549_CR4","first-page":"207","volume":"4","author":"E Jabbour","year":"2010","unstructured":"Jabbour E, Cortes J, Kantarjian H. Nilotinib for the treatment of chronic myeloid leukemia: an evidence-based review. Core Evid. 2010;4:207\u201313.","journal-title":"Core Evid"},{"issue":"Suppl 6","key":"2549_CR5","doi-asserted-by":"publisher","first-page":"vi42","DOI":"10.1093\/annonc\/mdm223","volume":"18","author":"A Olivieri","year":"2007","unstructured":"Olivieri A, Manzione L. Dasatinib: a new step in molecular target therapy. Ann Oncol. 2007;18(Suppl 6):vi42\u20136.","journal-title":"Ann Oncol"},{"issue":"2","key":"2549_CR6","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.leukres.2009.08.031","volume":"34","author":"M Breccia","year":"2010","unstructured":"Breccia M, Alimena G. Nilotinib: a second-generation tyrosine kinase inhibitor for chronic myeloid leukemia. Leuk Res. 2010;34(2):129\u201334.","journal-title":"Leuk Res"},{"issue":"4","key":"2549_CR7","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201707918","volume":"10","author":"M Jeitany","year":"2018","unstructured":"Jeitany M, Leroy C, Tosti P, Lafitte M, Le Guet J, Simon V, Bonenfant D, Robert B, Grillet F, Mollevi C, et al. Inhibition of DDR1-BCR signalling by nilotinib as a new therapeutic strategy for metastatic colorectal cancer. EMBO Mol Med. 2018;10(4): e7918.","journal-title":"EMBO Mol Med"},{"issue":"8","key":"2549_CR8","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1016\/j.cellsig.2006.02.012","volume":"18","author":"WF Vogel","year":"2006","unstructured":"Vogel WF, Abdulhussein R, Ford CE. Sensing extracellular matrix: an update on discoidin domain receptor function. Cell Signal. 2006;18(8):1108\u201316.","journal-title":"Cell Signal"},{"key":"2549_CR9","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.brainres.2010.03.099","volume":"1336","author":"B Roig","year":"2010","unstructured":"Roig B, Franco-Pons N, Martorell L, Tomas J, Vogel WF, Vilella E. Expression of the tyrosine kinase discoidin domain receptor 1 (DDR1) in human central nervous system myelin. Brain Res. 2010;1336:22\u20139.","journal-title":"Brain Res"},{"issue":"5","key":"2549_CR10","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1002\/jnr.21552","volume":"86","author":"MC Seo","year":"2008","unstructured":"Seo MC, Kim S, Kim SH, Zheng LT, Park EK, Lee WH, Suk K. Discoidin domain receptor 1 mediates collagen-induced inflammatory activation of microglia in culture. J Neurosci Res. 2008;86(5):1087\u201395.","journal-title":"J Neurosci Res"},{"issue":"22","key":"2549_CR11","doi-asserted-by":"publisher","first-page":"2374","DOI":"10.1182\/blood.2018882233","volume":"133","author":"N Hijiya","year":"2019","unstructured":"Hijiya N, Suttorp M. How I treat chronic myeloid leukemia in children and adolescents. Blood. 2019;133(22):2374\u201384.","journal-title":"Blood"},{"issue":"3","key":"2549_CR12","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1001\/jamaneurol.2019.4200","volume":"77","author":"FL Pagan","year":"2020","unstructured":"Pagan FL, Hebron ML, Wilmarth B, Torres-Yaghi Y, Lawler A, Mundel EE, Yusuf N, Starr NJ, Anjum M, Arellano J, et al. Nilotinib effects on safety, tolerability, and potential biomarkers in Parkinson disease: a phase 2 randomized clinical trial. JAMA Neurol. 2020;77(3):309\u201317.","journal-title":"JAMA Neurol"},{"issue":"3","key":"2549_CR13","doi-asserted-by":"publisher","first-page":"503","DOI":"10.3233\/JPD-160867","volume":"6","author":"F Pagan","year":"2016","unstructured":"Pagan F, Hebron M, Valadez EH, Torres-Yaghi Y, Huang X, Mills RR, Wilmarth BM, Howard H, Dunn C, Carlson A, et al. Nilotinib effects in Parkinson\u2019s disease and dementia with Lewy bodies. J Parkinsons Dis. 2016;6(3):503\u201317.","journal-title":"J Parkinsons Dis"},{"issue":"1","key":"2549_CR14","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1002\/ana.25775","volume":"88","author":"RS Turner","year":"2020","unstructured":"Turner RS, Hebron ML, Lawler A, Mundel EE, Yusuf N, Starr JN, Anjum M, Pagan F, Torres-Yaghi Y, Shi W, et al. Nilotinib effects on safety, tolerability, and biomarkers in Alzheimer\u2019s disease. Ann Neurol. 2020;88(1):183\u201394.","journal-title":"Ann Neurol"},{"key":"2549_CR15","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.neures.2015.01.004","volume":"96","author":"M Zhu","year":"2015","unstructured":"Zhu M, Xing D, Lu Z, Fan Y, Hou W, Dong H, Xiong L, Dong H. DDR1 may play a key role in destruction of the blood\u2013brain barrier after cerebral ischemia\u2013reperfusion. Neurosci Res. 2015;96:14\u20139.","journal-title":"Neurosci Res"},{"issue":"3","key":"2549_CR16","doi-asserted-by":"publisher","first-page":"329","DOI":"10.2174\/1871527315666160202125914","volume":"15","author":"J Leszek","year":"2016","unstructured":"Leszek J, Barreto GE, Gasiorowski K, Koutsouraki E, Avila-Rodrigues M, Aliev G. Inflammatory mechanisms and oxidative stress as key factors responsible for progression of neurodegeneration: role of brain innate immune system. CNS Neurol Disord Drug Targets. 2016;15(3):329\u201336.","journal-title":"CNS Neurol Disord Drug Targets"},{"issue":"37","key":"2549_CR17","doi-asserted-by":"publisher","first-page":"22805","DOI":"10.1074\/jbc.M115.659151","volume":"290","author":"Y Ishihara","year":"2015","unstructured":"Ishihara Y, Takemoto T, Itoh K, Ishida A, Yamazaki T. Dual role of superoxide dismutase 2 induced in activated microglia: oxidative stress tolerance and convergence of inflammatory responses. J Biol Chem. 2015;290(37):22805\u201317.","journal-title":"J Biol Chem"},{"issue":"1","key":"2549_CR18","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s12974-017-1038-8","volume":"15","author":"JJ Li","year":"2018","unstructured":"Li JJ, Wang B, Kodali MC, Chen C, Kim E, Patters BJ, Lan L, Kumar S, Wang X, Yue J, et al. In vivo evidence for the contribution of peripheral circulating inflammatory exosomes to neuroinflammation. J Neuroinflamm. 2018;15(1):8.","journal-title":"J Neuroinflamm"},{"issue":"Suppl 1","key":"2549_CR19","doi-asserted-by":"publisher","first-page":"S28","DOI":"10.1053\/j.seminoncol.2011.01.014","volume":"38","author":"J Trent","year":"2011","unstructured":"Trent J, Molimard M. Pharmacokinetics and pharmacodynamics of nilotinib in gastrointestinal stromal tumors. Semin Oncol. 2011;38(Suppl 1):S28-33.","journal-title":"Semin Oncol"},{"issue":"1","key":"2549_CR20","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, Lee SM, Lee JY, Jeong YJ, Nam HW, et al. Dasatinib regulates LPS-induced microglial and astrocytic neuroinflammatory responses by inhibiting AKT\/STAT3 signaling. J Neuroinflamm. 2019;16(1):190.","journal-title":"J Neuroinflamm"},{"key":"2549_CR21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.684344","volume":"12","author":"J Kim","year":"2021","unstructured":"Kim J, Park JH, Park SK, Hoe HS. Sorafenib modulates the LPS- and Abeta-induced neuroinflammatory response in cells, wild-type mice, and 5xFAD mice. Front Immunol. 2021;12: 684344.","journal-title":"Front Immunol"},{"issue":"3","key":"2549_CR22","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13332","volume":"20","author":"HJ Lee","year":"2021","unstructured":"Lee HJ, Jeon SG, Kim J, Kang RJ, Kim SM, Han KM, Park H, Kim KT, Sung YM, Nam HY, et al. Ibrutinib modulates Abeta\/tau pathology, neuroinflammation, and cognitive function in mouse models of Alzheimer\u2019s disease. Aging Cell. 2021;20(3): e13332.","journal-title":"Aging Cell"},{"key":"2549_CR23","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.neuroscience.2015.07.070","volume":"304","author":"I Lonskaya","year":"2015","unstructured":"Lonskaya I, Hebron ML, Selby ST, Turner RS, Moussa CE. Nilotinib and bosutinib modulate pre-plaque alterations of blood immune markers and neuro-inflammation in Alzheimer\u2019s disease models. Neuroscience. 2015;304:316\u201327.","journal-title":"Neuroscience"},{"key":"2549_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108025","volume":"99","author":"J Wu","year":"2021","unstructured":"Wu J, Xu X, Zheng L, Mo J, Jin X, Bao Y. Nilotinib inhibits microglia-mediated neuroinflammation to protect against dopaminergic neuronal death in Parkinson\u2019s disease models. Int Immunopharmacol. 2021;99: 108025.","journal-title":"Int Immunopharmacol"},{"key":"2549_CR25","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.neulet.2014.10.016","volume":"584","author":"J Park","year":"2015","unstructured":"Park J, Min JS, Kim B, Chae UB, Yun JW, Choi MS, Kong IK, Chang KT, Lee DS. Mitochondrial ROS govern the LPS-induced pro-inflammatory response in microglia cells by regulating MAPK and NF-kappaB pathways. Neurosci Lett. 2015;584:191\u20136.","journal-title":"Neurosci Lett"},{"issue":"5","key":"2549_CR26","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1007\/s00702-021-02331-1","volume":"128","author":"Y Zhang","year":"2021","unstructured":"Zhang Y, Anoopkumar-Dukie S, Mallik SB, Davey AK. SIRT1 and SIRT2 modulators reduce LPS-induced inflammation in HAPI microglial cells and protect SH-SY5Y neuronal cells in vitro. J Neural Transm (Vienna). 2021;128(5):631\u201344.","journal-title":"J Neural Transm (Vienna)"},{"issue":"2","key":"2549_CR27","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/S0006-8993(97)01215-8","volume":"780","author":"B Hauss-Wegrzyniak","year":"1998","unstructured":"Hauss-Wegrzyniak B, Dobrzanski P, Stoehr JD, Wenk GL. Chronic neuroinflammation in rats reproduces components of the neurobiology of Alzheimer\u2019s disease. Brain Res. 1998;780(2):294\u2013303.","journal-title":"Brain Res"},{"key":"2549_CR28","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.jneuroim.2016.10.004","volume":"300","author":"N Behairi","year":"2016","unstructured":"Behairi N, Belkhelfa M, Rafa H, Labsi M, Deghbar N, Bouzid N, Mesbah-Amroun H, Touil-Boukoffa C. All-trans retinoic acid (ATRA) prevents lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment in aged rats. J Neuroimmunol. 2016;300:21\u20139.","journal-title":"J Neuroimmunol"},{"key":"2549_CR29","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/1742-2094-5-37","volume":"5","author":"JW Lee","year":"2008","unstructured":"Lee JW, Lee YK, Yuk DY, Choi DY, Ban SB, Oh KW, Hong JT. Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. J Neuroinflamm. 2008;5:37.","journal-title":"J Neuroinflamm"},{"issue":"3","key":"2549_CR30","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1111\/j.1460-9568.2011.07764.x","volume":"34","author":"AD Roe","year":"2011","unstructured":"Roe AD, Staup MA, Serrats J, Sawchenko PE, Rissman RA. Lipopolysaccharide-induced tau phosphorylation and kinase activity-modulation, but not mediation, by corticotropin-releasing factor receptors. Eur J Neurosci. 2011;34(3):448\u201356.","journal-title":"Eur J Neurosci"},{"key":"2549_CR31","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.nbd.2017.08.009","volume":"108","author":"EE Beier","year":"2017","unstructured":"Beier EE, Neal M, Alam G, Edler M, Wu LJ, Richardson JR. Alternative microglial activation is associated with cessation of progressive dopamine neuron loss in mice systemically administered lipopolysaccharide. Neurobiol Dis. 2017;108:115\u201327.","journal-title":"Neurobiol Dis"},{"issue":"5","key":"2549_CR32","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/j.neuro.2008.02.014","volume":"29","author":"Y Liu","year":"2008","unstructured":"Liu Y, Qin L, Wilson B, Wu X, Qian L, Granholm AC, Crews FT, Hong JS. Endotoxin induces a delayed loss of TH-IR neurons in substantia nigra and motor behavioral deficits. Neurotoxicology. 2008;29(5):864\u201370.","journal-title":"Neurotoxicology"},{"issue":"22","key":"2549_CR33","doi-asserted-by":"publisher","first-page":"10588","DOI":"10.1093\/nar\/gkv1166","volume":"43","author":"K Mahajan","year":"2015","unstructured":"Mahajan K, Mahajan NP. Cross talk of tyrosine kinases with the DNA damage signaling pathways. Nucleic Acids Res. 2015;43(22):10588\u2013601.","journal-title":"Nucleic Acids Res"},{"key":"2549_CR34","doi-asserted-by":"publisher","first-page":"543","DOI":"10.3389\/fphar.2019.00543","volume":"10","author":"GJ Song","year":"2019","unstructured":"Song GJ, Rahman MH, Jha MK, Gupta DP, Park SH, Kim JH, Lee SH, Lee IK, Sim T, Bae YC, et al. A Bcr-Abl inhibitor GNF-2 attenuates inflammatory activation of glia and chronic pain. Front Pharmacol. 2019;10:543.","journal-title":"Front Pharmacol"},{"issue":"6","key":"2549_CR35","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.4049\/jimmunol.1801616","volume":"203","author":"AA Bohio","year":"2019","unstructured":"Bohio AA, Sattout A, Wang R, Wang K, Sah RK, Guo X, Zeng X, Ke Y, Boldogh I, Ba X. c-Abl-mediated tyrosine phosphorylation of PARP1 is crucial for expression of proinflammatory genes. J Immunol. 2019;203(6):1521\u201331.","journal-title":"J Immunol"},{"key":"2549_CR36","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.754123","volume":"13","author":"J Kim","year":"2021","unstructured":"Kim J, Park JH, Shah K, Mitchell SJ, Cho K, Hoe HS. The anti-diabetic drug gliquidone modulates lipopolysaccharide-mediated microglial neuroinflammatory responses by inhibiting the NLRP3 inflammasome. Front Aging Neurosci. 2021;13: 754123.","journal-title":"Front Aging Neurosci"},{"issue":"9","key":"2549_CR37","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.3390\/cells9091982","volume":"9","author":"H Park","year":"2020","unstructured":"Park H, Han KM, Jeon H, Lee JS, Lee H, Jeon SG, Park JH, Kim YG, Lin Y, Lee YH, et al. The MAO inhibitor tranylcypromine alters LPS- and Abeta-mediated neuroinflammatory responses in wild-type mice and a mouse model of AD. Cells. 2020;9(9):1982.","journal-title":"Cells"},{"issue":"10","key":"2549_CR38","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1517\/17425255.4.10.1265","volume":"4","author":"GJ Harry","year":"2008","unstructured":"Harry GJ, Kraft AD. Neuroinflammation and microglia: considerations and approaches for neurotoxicity assessment. Expert Opin Drug Metab Toxicol. 2008;4(10):1265\u201377.","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"1","key":"2549_CR39","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.cyto.2012.05.022","volume":"60","author":"MA Montano","year":"2012","unstructured":"Montano MA, da Cruz IB, Duarte MM, Krewer Cda C, da Rocha MI, Manica-Cattani MF, Soares FA, Rosa G, Maris AF, Battiston FG, et al. Inflammatory cytokines in vitro production are associated with Ala16Val superoxide dismutase gene polymorphism of peripheral blood mononuclear cells. Cytokine. 2012;60(1):30\u20133.","journal-title":"Cytokine"},{"issue":"2","key":"2549_CR40","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.taap.2011.03.023","volume":"253","author":"DS El-Agamy","year":"2011","unstructured":"El-Agamy DS. Nilotinib ameliorates lipopolysaccharide-induced acute lung injury in rats. Toxicol Appl Pharmacol. 2011;253(2):153\u201360.","journal-title":"Toxicol Appl Pharmacol"},{"issue":"13","key":"2549_CR41","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.1093\/hmg\/ddy143","volume":"27","author":"S Lee","year":"2018","unstructured":"Lee S, Kim S, Park YJ, Yun SP, Kwon SH, Kim D, Kim DY, Shin JS, Cho DJ, Lee GY, et al. The c-Abl inhibitor, radotinib HCl, is neuroprotective in a preclinical Parkinson\u2019s disease mouse model. Hum Mol Genet. 2018;27(13):2344\u201356.","journal-title":"Hum Mol Genet"},{"issue":"2","key":"2549_CR42","doi-asserted-by":"publisher","first-page":"146","DOI":"10.5114\/fn.2019.84423","volume":"57","author":"GM Attia","year":"2019","unstructured":"Attia GM, Elmansy RA, Elsaed WM. Neuroprotective effect of nilotinib on pentylenetetrazol-induced epilepsy in adult rat hippocampus: involvement of oxidative stress, autophagy, inflammation, and apoptosis. Folia Neuropathol. 2019;57(2):146\u201360.","journal-title":"Folia Neuropathol"},{"issue":"1","key":"2549_CR43","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s12974-020-1728-5","volume":"17","author":"Z Zhao","year":"2020","unstructured":"Zhao Z, Wang Y, Zhou R, Li Y, Gao Y, Tu D, Wilson B, Song S, Feng J, Hong JS, et al. A novel role of NLRP3-generated IL-1beta in the acute-chronic transition of peripheral lipopolysaccharide-elicited neuroinflammation: implications for sepsis-associated neurodegeneration. J Neuroinflamm. 2020;17(1):64.","journal-title":"J Neuroinflamm"},{"issue":"2","key":"2549_CR44","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1002\/glia.22930","volume":"64","author":"DM Norden","year":"2016","unstructured":"Norden DM, Trojanowski PJ, Villanueva E, Navarro E, Godbout JP. Sequential activation of microglia and astrocyte cytokine expression precedes increased Iba-1 or GFAP immunoreactivity following systemic immune challenge. Glia. 2016;64(2):300\u201316.","journal-title":"Glia"},{"issue":"4","key":"2549_CR45","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/j.jhep.2012.05.012","volume":"57","author":"LM Ocuin","year":"2012","unstructured":"Ocuin LM, Zeng S, Cavnar MJ, Sorenson EC, Bamboat ZM, Greer JB, Kim TS, Popow R, DeMatteo RP. Nilotinib protects the murine liver from ischemia\/reperfusion injury. J Hepatol. 2012;57(4):766\u201373.","journal-title":"J Hepatol"},{"issue":"1","key":"2549_CR46","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.jid.2017.07.839","volume":"138","author":"J Delyon","year":"2018","unstructured":"Delyon J, Chevret S, Jouary T, Dalac S, Dalle S, Guillot B, Arnault JP, Avril MF, Bedane C, Bens G, et al. STAT3 mediates nilotinib response in KIT-altered melanoma: a phase II multicenter trial of the French skin cancer network. J Invest Dermatol. 2018;138(1):58\u201367.","journal-title":"J Invest Dermatol"},{"issue":"1","key":"2549_CR47","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.ajpath.2011.03.023","volume":"179","author":"D Guerrot","year":"2011","unstructured":"Guerrot D, Kerroch M, Placier S, Vandermeersch S, Trivin C, Mael-Ainin M, Chatziantoniou C, Dussaule JC. Discoidin domain receptor 1 is a major mediator of inflammation and fibrosis in obstructive nephropathy. Am J Pathol. 2011;179(1):83\u201391.","journal-title":"Am J Pathol"},{"key":"2549_CR48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jneuroim.2017.07.009","volume":"311","author":"M Hebron","year":"2017","unstructured":"Hebron M, Peyton M, Liu X, Gao X, Wang R, Lonskaya I, Moussa CE. Discoidin domain receptor inhibition reduces neuropathology and attenuates inflammation in neurodegeneration models. J Neuroimmunol. 2017;311:1\u20139.","journal-title":"J Neuroimmunol"},{"issue":"6","key":"2549_CR49","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000633","volume":"7","author":"AJ Fowler","year":"2021","unstructured":"Fowler AJ, Ahn J, Hebron M, Chiu T, Ayoub R, Mulki S, Ressom H, Torres-Yaghi Y, Wilmarth B, Pagan FL, et al. CSF microRNAs reveal impairment of angiogenesis and autophagy in Parkinson disease. Neurol Genet. 2021;7(6): e633.","journal-title":"Neurol Genet"},{"issue":"19","key":"2549_CR50","doi-asserted-by":"publisher","first-page":"7611","DOI":"10.1073\/pnas.86.19.7611","volume":"86","author":"WS Griffin","year":"1989","unstructured":"Griffin WS, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White CL 3rd, Araoz C. Brain interleukin 1 and S-100 immunoreactivity are elevated in down syndrome and Alzheimer disease. Proc Natl Acad Sci USA. 1989;86(19):7611\u20135.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1\u20132","key":"2549_CR51","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/S0166-4328(02)00043-8","volume":"134","author":"RM Barrientos","year":"2002","unstructured":"Barrientos RM, Higgins EA, Sprunger DB, Watkins LR, Rudy JW, Maier SF. Memory for context is impaired by a post context exposure injection of interleukin-1 beta into dorsal hippocampus. Behav Brain Res. 2002;134(1\u20132):291\u20138.","journal-title":"Behav Brain Res"},{"issue":"6","key":"2549_CR52","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1194\/jlr.M300526-JLR200","volume":"45","author":"C Song","year":"2004","unstructured":"Song C, Horrobin D. Omega-3 fatty acid ethyl-eicosapentaenoate, but not soybean oil, attenuates memory impairment induced by central IL-1beta administration. J Lipid Res. 2004;45(6):1112\u201321.","journal-title":"J Lipid Res"},{"issue":"1","key":"2549_CR53","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/0006-8993(93)90468-3","volume":"613","author":"MS Oitzl","year":"1993","unstructured":"Oitzl MS, van Oers H, Schobitz B, de Kloet ER. Interleukin-1 beta, but not interleukin-6, impairs spatial navigation learning. Brain Res. 1993;613(1):160\u20133.","journal-title":"Brain Res"},{"issue":"2","key":"2549_CR54","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.bbi.2009.10.002","volume":"24","author":"AM Hein","year":"2010","unstructured":"Hein AM, Stasko MR, Matousek SB, Scott-McKean JJ, Maier SF, Olschowka JA, Costa AC, O\u2019Banion MK. Sustained hippocampal IL-1beta overexpression impairs contextual and spatial memory in transgenic mice. Brain Behav Immun. 2010;24(2):243\u201353.","journal-title":"Brain Behav Immun"},{"key":"2549_CR55","doi-asserted-by":"publisher","first-page":"33427","DOI":"10.1038\/srep33427","volume":"6","author":"H Nishioka","year":"2016","unstructured":"Nishioka H, Tooi N, Isobe T, Nakatsuji N, Aiba K. BMS-708163 and nilotinib restore synaptic dysfunction in human embryonic stem cell-derived Alzheimer\u2019s disease models. Sci Rep. 2016;6:33427.","journal-title":"Sci Rep"},{"issue":"11","key":"2549_CR56","doi-asserted-by":"publisher","first-page":"E480","DOI":"10.1002\/ajh.24495","volume":"91","author":"S Claudiani","year":"2016","unstructured":"Claudiani S, Apperley JF, Deplano S, Khorashad J, Foroni L, Palanicawandar R, Perry R, Milojkovic D. Cognitive dysfunction after withdrawal of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia. Am J Hematol. 2016;91(11):E480\u20131.","journal-title":"Am J Hematol"},{"key":"2549_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2021.102031","volume":"202","author":"L La Barbera","year":"2021","unstructured":"La Barbera L, Vedele F, Nobili A, Krashia P, Spoleti E, Latagliata EC, Cutuli D, Cauzzi E, Marino R, Viscomi MT, et al. Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer\u2019s disease. Prog Neurobiol. 2021;202: 102031.","journal-title":"Prog Neurobiol"},{"issue":"1","key":"2549_CR58","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/s41467-017-02751-2","volume":"9","author":"AC Frank","year":"2018","unstructured":"Frank AC, Huang S, Zhou M, Gdalyahu A, Kastellakis G, Silva TK, Lu E, Wen X, Poirazi P, Trachtenberg JT, et al. Hotspots of dendritic spine turnover facilitate clustered spine addition and learning and memory. Nat Commun. 2018;9(1):422.","journal-title":"Nat Commun"},{"issue":"17","key":"2549_CR59","doi-asserted-by":"publisher","first-page":"7963","DOI":"10.1073\/pnas.0914613107","volume":"107","author":"S Tronel","year":"2010","unstructured":"Tronel S, Fabre A, Charrier V, Oliet SH, Gage FH, Abrous DN. Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons. Proc Natl Acad Sci USA. 2010;107(17):7963\u20138.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"2549_CR60","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab125","volume":"3","author":"DD Jobson","year":"2021","unstructured":"Jobson DD, Hase Y, Clarkson AN, Kalaria RN. The role of the medial prefrontal cortex in cognition, ageing and dementia. Brain Commun. 2021;3(3): fcab125.","journal-title":"Brain Commun"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-022-02549-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-022-02549-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-022-02549-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T14:12:17Z","timestamp":1657894337000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-022-02549-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,15]]},"references-count":60,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["2549"],"URL":"https:\/\/doi.org\/10.1186\/s12974-022-02549-0","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,15]]},"assertion":[{"value":"4 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2022","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) and performed in accordance with approved animal protocols of the Korea Brain Research Institute (KBRI, approval no. IACUC-21-00021).","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 have no competing interests to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"187"}}