{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:08:36Z","timestamp":1792757316567,"version":"4.5.0"},"reference-count":86,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1007\/s12035-026-06004-6","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T07:38:51Z","timestamp":1781941131000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["LPS-Induced Neuroinflammation in Neurodegenerative Diseases: A Double-Edged Sword?"],"prefix":"10.1007","volume":"63","author":[{"given":"Alaleh","family":"Mohammadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Aghajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morteza","family":"Alipour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avin","family":"Ghorbani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samim Momennejad","family":"Limoodehi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8277-9841","authenticated-orcid":false,"given":"Mojtaba Hedayati","family":"Ch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,20]]},"reference":[{"key":"6004_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07830","author":"BS Park","year":"2009","unstructured":"Park BS et al (2009) The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature. https:\/\/doi.org\/10.1038\/nature07830","journal-title":"Nature"},{"key":"6004_CR2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2013.00003","author":"N Maeshima","year":"2013","unstructured":"Maeshima N, Fernandez RC (2013) Recognition of lipid A variants by the TLR4-MD-2 receptor complex. Front Cell Infect Microbiol. https:\/\/doi.org\/10.3389\/fcimb.2013.00003","journal-title":"Front Cell Infect Microbiol"},{"key":"6004_CR3","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3638","author":"JG Walsh","year":"2014","unstructured":"Walsh JG, Muruve DA, Power C (2014) Inflammasomes in the CNS. Nat Rev Neurosci. https:\/\/doi.org\/10.1038\/nrn3638","journal-title":"Nat Rev Neurosci"},{"key":"6004_CR4","doi-asserted-by":"publisher","DOI":"10.3390\/cells9071717","author":"JA Rodr\u00edguez-G\u00f3mez","year":"2020","unstructured":"Rodr\u00edguez-G\u00f3mez JA et al (2020) Microglia: agents of the CNS pro-inflammatory response. Cells. https:\/\/doi.org\/10.3390\/cells9071717","journal-title":"Cells"},{"key":"6004_CR5","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20767","author":"T Kielian","year":"2006","unstructured":"Kielian T (2006) Toll-like receptors in central nervous system glial inflammation and homeostasis. J Neurosci Res. https:\/\/doi.org\/10.1002\/jnr.20767","journal-title":"J Neurosci Res"},{"key":"6004_CR6","doi-asserted-by":"publisher","DOI":"10.3390\/cells12101418","author":"E Xingi","year":"2023","unstructured":"Xingi E et al (2023) LPS-induced systemic inflammation affects the dynamic interactions of astrocytes and microglia with the vasculature of the mouse brain cortex. Cells. https:\/\/doi.org\/10.3390\/cells12101418","journal-title":"Cells"},{"key":"6004_CR7","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1141-5","author":"Y Liu","year":"2018","unstructured":"Liu Y et al (2018) Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice. J Neuroinflammation. https:\/\/doi.org\/10.1186\/s12974-018-1141-5","journal-title":"J Neuroinflammation"},{"key":"6004_CR8","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20467","author":"L Qin","year":"2007","unstructured":"Qin L et al (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia. https:\/\/doi.org\/10.1002\/glia.20467","journal-title":"Glia"},{"key":"6004_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-150","author":"MA Erickson","year":"2012","unstructured":"Erickson MA et al (2012) Lipopolysaccharide impairs amyloid beta efflux from brain: altered vascular sequestration, cerebrospinal fluid reabsorption, peripheral clearance and transporter function at the blood-brain barrier. J Neuroinflammation. https:\/\/doi.org\/10.1186\/1742-2094-9-150","journal-title":"J Neuroinflammation"},{"key":"6004_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-024-00722-y","author":"GC Brown","year":"2024","unstructured":"Brown GC, Heneka MT (2024) The endotoxin hypothesis of Alzheimer\u2019s disease. Mol Neurodegener. https:\/\/doi.org\/10.1186\/s13024-024-00722-y","journal-title":"Mol Neurodegener"},{"key":"6004_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1769-z","author":"C Ising","year":"2019","unstructured":"Ising C et al (2019) NLRP3 inflammasome activation drives tau pathology. Nature. https:\/\/doi.org\/10.1038\/s41586-019-1769-z","journal-title":"Nature"},{"key":"6004_CR12","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12644","author":"P La Vitola","year":"2021","unstructured":"La Vitola P et al (2021) Peripheral inflammation exacerbates \u03b1-synuclein toxicity and neuropathology in Parkinson\u2019s models. Neuropathol Appl Neurobiol. https:\/\/doi.org\/10.1111\/nan.12644","journal-title":"Neuropathol Appl Neurobiol"},{"key":"6004_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0023-4","author":"AC Wendeln","year":"2018","unstructured":"Wendeln AC et al (2018) Innate immune memory in the brain shapes neurological disease hallmarks. Nature. https:\/\/doi.org\/10.1038\/s41586-018-0023-4","journal-title":"Nature"},{"key":"6004_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0434-1","author":"WA Banks","year":"2015","unstructured":"Banks WA et al (2015) Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit. J Neuroinflammation. https:\/\/doi.org\/10.1186\/s12974-015-0434-1","journal-title":"J Neuroinflammation"},{"key":"6004_CR15","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2018","author":"JF Cryan","year":"2019","unstructured":"Cryan JF et al (2019) The microbiota-gut-brain axis. Physiol Rev. https:\/\/doi.org\/10.1152\/physrev.00018.2018","journal-title":"Physiol Rev"},{"key":"6004_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.03.010","author":"A Varatharaj","year":"2017","unstructured":"Varatharaj A, Galea I (2017) The blood-brain barrier in systemic inflammation. Brain Behav Immun. https:\/\/doi.org\/10.1016\/j.bbi.2016.03.010","journal-title":"Brain Behav Immun"},{"key":"6004_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30356-4","author":"JF Cryan","year":"2020","unstructured":"Cryan JF, O\u2019Riordan KJ, Sandhu K, Peterson V, Dinan TG (2020) The gut microbiome in neurological disorders. Lancet Neurol. https:\/\/doi.org\/10.1016\/S1474-4422(19)30356-4","journal-title":"Lancet Neurol"},{"key":"6004_CR18","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 et al (2015) Neuroinflammation in Alzheimer\u2019s disease. Lancet Neurol 14:388\u2013405. https:\/\/doi.org\/10.1016\/S1474-4422(15)70016-5","journal-title":"Lancet Neurol"},{"key":"6004_CR19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06736.x","author":"MM Buchanan","year":"2010","unstructured":"Buchanan MM, Hutchinson M, Watkins LR, Yin H (2010) Toll-like receptor 4 in CNS pathologies. J Neurochem. https:\/\/doi.org\/10.1111\/j.1471-4159.2010.06736.x","journal-title":"J Neurochem"},{"key":"6004_CR20","doi-asserted-by":"publisher","unstructured":"O'Sullivan SA, O'Sullivan C, Healy LM, Dev KK, Sheridan GK (2018) Sphingosine 1-phosphate receptors regulate TLR4-induced CXCL5 release from astrocytes and microglia. J Neurochem 144(6):736\u2013747. https:\/\/doi.org\/10.1111\/jnc.14313","DOI":"10.1111\/jnc.14313"},{"key":"6004_CR21","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0332-6","author":"ICM Hoogland","year":"2015","unstructured":"Hoogland ICM, Houbolt C, van Westerloo DJ, van Gool WA, van de Beek D (2015) Systemic inflammation and microglial activation: systematic review of animal experiments. J Neuroinflamm. https:\/\/doi.org\/10.1186\/s12974-015-0332-6","journal-title":"J Neuroinflamm"},{"key":"6004_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1863","author":"T Kawai","year":"2010","unstructured":"Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on toll-like receptors. Nat Immunol. https:\/\/doi.org\/10.1038\/ni.1863","journal-title":"Nat Immunol"},{"key":"6004_CR23","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031023","author":"KA Fitzgerald","year":"2003","unstructured":"Fitzgerald KA et al (2003) LPS-TLR4 signaling to IRF-3\/7 and NF-\u03baB involves the toll adapters TRAM and TRIF. J Exp Med. https:\/\/doi.org\/10.1084\/jem.20031023","journal-title":"J Exp Med"},{"key":"6004_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.01.022","author":"T Miyake","year":"2014","unstructured":"Miyake T et al (2014) TRPM2 contributes to LPS\/IFN\u03b3-induced production of nitric oxide via the p38\/JNK pathway in microglia. Biochem Biophys Res Commun. https:\/\/doi.org\/10.1016\/j.bbrc.2014.01.022","journal-title":"Biochem Biophys Res Commun"},{"key":"6004_CR25","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-015-9623-z","author":"H Badshah","year":"2016","unstructured":"Badshah H et al (2016) Protective effect of lupeol against lipopolysaccharide-induced neuroinflammation via the p38\/c-Jun N-terminal kinase pathway in the adult mouse brain. J Neuroimmune Pharmacol. https:\/\/doi.org\/10.1007\/s11481-015-9623-z","journal-title":"J Neuroimmune Pharmacol"},{"key":"6004_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1857","author":"F Martinon","year":"2010","unstructured":"Martinon F, Chen X, Lee AH, Glimcher LH (2010) TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nat Immunol. https:\/\/doi.org\/10.1038\/ni.1857","journal-title":"Nat Immunol"},{"key":"6004_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08722-3","author":"C Pintado","year":"2017","unstructured":"Pintado C, MacI\u00e1s S, Dom\u00ednguez-Mart\u00edn H, Castan\u00f5 A, Ruano D (2017) Neuroinflammation alters cellular proteostasis by producing endoplasmic reticulum stress, autophagy activation and disrupting ERAD activation. Sci Rep. https:\/\/doi.org\/10.1038\/s41598-017-08722-3","journal-title":"Sci Rep"},{"key":"6004_CR28","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0183-y","author":"NT Sprenkle","year":"2017","unstructured":"Sprenkle NT, Sims SG, S\u00e1nchez CL, Meares GP (2017) Endoplasmic reticulum stress and inflammation in the central nervous system. Mol Neurodegener. https:\/\/doi.org\/10.1186\/s13024-017-0183-y","journal-title":"Mol Neurodegener"},{"key":"6004_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.08.008","author":"DN Bronner","year":"2015","unstructured":"Bronner DN et al (2015) Endoplasmic reticulum stress activates the inflammasome via NLRP3- and caspase-2-driven mitochondrial damage. Immunity. https:\/\/doi.org\/10.1016\/j.immuni.2015.08.008","journal-title":"Immunity"},{"key":"6004_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2011.10.011","author":"S Huang","year":"2012","unstructured":"Huang S et al (2012) The putative tumor suppressor Zc3h12d modulates toll-like receptor signaling in macrophages. Cell Signal. https:\/\/doi.org\/10.1016\/j.cellsig.2011.10.011","journal-title":"Cell Signal"},{"key":"6004_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2015.05.018","author":"H Zhang","year":"2015","unstructured":"Zhang H et al (2015) ZC3H12D attenuated inflammation responses by reducing mRNA stability of proinflammatory genes. Mol Immunol. https:\/\/doi.org\/10.1016\/j.molimm.2015.05.018","journal-title":"Mol Immunol"},{"key":"6004_CR32","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251086","author":"S Saeed","year":"2014","unstructured":"Saeed S et al (2014) Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science. https:\/\/doi.org\/10.1126\/science.1251086","journal-title":"Science"},{"key":"6004_CR33","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.910988","author":"E Brandi","year":"2022","unstructured":"Brandi E et al (2022) Brain region-specific microglial and astrocytic activation in response to systemic lipopolysaccharides exposure. Front Aging Neurosci. https:\/\/doi.org\/10.3389\/fnagi.2022.910988","journal-title":"Front Aging Neurosci"},{"key":"6004_CR34","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22930","author":"DM Norden","year":"2016","unstructured":"Norden DM, Trojanowski PJ, Villanueva E, Navarro E, Godbout JP (2016) Sequential activation of microglia and astrocyte cytokine expression precedes increased iba-1 or GFAP immunoreactivity following systemic immune challenge. Glia. https:\/\/doi.org\/10.1002\/glia.22930","journal-title":"Glia"},{"key":"6004_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029","author":"SA Liddelow","year":"2017","unstructured":"Liddelow SA et al (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature. https:\/\/doi.org\/10.1038\/nature21029","journal-title":"Nature"},{"key":"6004_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01628-9","author":"A Verkhratsky","year":"2023","unstructured":"Verkhratsky A et al (2023) Astrocytes in human central nervous system diseases: a frontier for new therapies. Sig Transduct Target Ther. https:\/\/doi.org\/10.1038\/s41392-023-01628-9","journal-title":"Sig Transduct Target Ther"},{"key":"6004_CR37","unstructured":"Wang LM, Wu Q, Kirk RA et al (2018) Lipopolysaccharide endotoxemia induces amyloid-\u03b2 and p-tau formation in the rat brain. Am J Nucl Med Mol Imaging 8(2):86\u201399"},{"key":"6004_CR38","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00042","author":"X Zhan","year":"2018","unstructured":"Zhan X, Stamova B, Sharp FR (2018) Lipopolysaccharide associates with amyloid plaques, neurons and oligodendrocytes in Alzheimer\u2019s disease brain: a review. Front Aging Neurosci. https:\/\/doi.org\/10.3389\/fnagi.2018.00042","journal-title":"Front Aging Neurosci"},{"key":"6004_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/s1382-6689(97)10004-7","author":"T Minami","year":"1998","unstructured":"Minami T et al (1998) Roles of nitric oxide and prostaglandins in the increased permeability of the blood-brain barrier caused by lipopolysaccharide. Environ Toxicol Pharmacol. https:\/\/doi.org\/10.1016\/s1382-6689(97)10004-7","journal-title":"Environ Toxicol Pharmacol"},{"key":"6004_CR40","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.bbi.2015.03.013","volume":"48","author":"W Schaafsma","year":"2015","unstructured":"Schaafsma W et al (2015) Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing. Brain Behav Immun 48:205\u2013221","journal-title":"Brain Behav Immun"},{"key":"6004_CR41","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2014.10.016","author":"J Park","year":"2015","unstructured":"Park J et al (2015) Mitochondrial ROS govern the LPS-induced pro-inflammatory response in microglia cells by regulating MAPK and NF-\u03baB pathways. Neurosci Lett. https:\/\/doi.org\/10.1016\/j.neulet.2014.10.016","journal-title":"Neurosci Lett"},{"key":"6004_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2023.11.009","author":"GH Schirmbeck","year":"2023","unstructured":"Schirmbeck GH et al (2023) Long-term LPS systemic administration leads to memory impairment and disturbance in astrocytic homeostasis. Neurotoxicology. https:\/\/doi.org\/10.1016\/j.neuro.2023.11.009","journal-title":"Neurotoxicology"},{"key":"6004_CR43","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-1728-5","author":"Z Zhao","year":"2020","unstructured":"Zhao Z et al (2020) A novel role of NLRP3-generated IL-1\u03b2 in the acute-chronic transition of peripheral lipopolysaccharide-elicited neuroinflammation: implications for sepsis-associated neurodegeneration. J Neuroinflammation. https:\/\/doi.org\/10.1186\/s12974-020-1728-5","journal-title":"J Neuroinflammation"},{"key":"6004_CR44","doi-asserted-by":"publisher","DOI":"10.3390\/toxins17060293","author":"MP dos Santos","year":"2025","unstructured":"dos Santos MP et al (2025) Lipopolysaccharide induces mitochondrial fragmentation and energetic shift in reactive microglia: evidence for a cell-autonomous program of metabolic plasticity. Toxins (Basel). https:\/\/doi.org\/10.3390\/toxins17060293","journal-title":"Toxins (Basel)"},{"key":"6004_CR45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0306906101","author":"TL Gioannini","year":"2004","unstructured":"Gioannini TL et al (2004) Isolation of an endotoxin-MD-2 complex that produces Toll-like receptor 4-dependent cell activation at picomolar concentrations. Proc Natl Acad Sci U S A. https:\/\/doi.org\/10.1073\/pnas.0306906101","journal-title":"Proc Natl Acad Sci U S A"},{"key":"6004_CR46","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.308067","author":"H Mizobuchi","year":"2021","unstructured":"Mizobuchi H, Soma GI (2021) Low-dose lipopolysaccharide as an immune regulator for homeostasis maintenance in the central nervous system through transformation to neuroprotective microglia. Neural Regen Res. https:\/\/doi.org\/10.4103\/1673-5374.308067","journal-title":"Neural Regen Res"},{"key":"6004_CR47","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03198-1","author":"J Kim","year":"2024","unstructured":"Kim J et al (2024) Repeated LPS induces training and tolerance of microglial responses across brain regions. J Neuroinflammation. https:\/\/doi.org\/10.1186\/s12974-024-03198-1","journal-title":"J Neuroinflammation"},{"key":"6004_CR48","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20092293","author":"CRA Batista","year":"2019","unstructured":"Batista CRA, Gomes GF, Candelario-Jalil E, Fiebich BL, de Oliveira ACP (2019) Lipopolysaccharide-induced neuroinflammation as a bridge to understand neurodegeneration. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms20092293","journal-title":"Int J Mol Sci"},{"key":"6004_CR49","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-025-02149-4","author":"R Luo","year":"2025","unstructured":"Luo R, Yao Y, Chen Z, Sun X (2025) An examination of the LPS-TLR4 immune response through the analysis of molecular structures and protein\u2013protein interactions. Cell Commun Signal. https:\/\/doi.org\/10.1186\/s12964-025-02149-4","journal-title":"Cell Commun Signal"},{"key":"6004_CR50","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-9070-5","author":"Y Tang","year":"2016","unstructured":"Tang Y, Le W (2016) Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol Neurobiol. https:\/\/doi.org\/10.1007\/s12035-014-9070-5","journal-title":"Mol Neurobiol"},{"key":"6004_CR51","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.18.2335","author":"JL Cummings","year":"2002","unstructured":"Cummings JL, Cole G (2002) Alzheimer disease. JAMA. https:\/\/doi.org\/10.1001\/jama.287.18.2335","journal-title":"JAMA"},{"key":"6004_CR52","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.5847","author":"GS Bloom","year":"2014","unstructured":"Bloom GS (2014) Amyloid-\u03b2 and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurol. https:\/\/doi.org\/10.1001\/jamaneurol.2013.5847","journal-title":"JAMA Neurol"},{"key":"6004_CR53","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2018.04.22","author":"J-W Li","year":"2018","unstructured":"Li J-W, Zong Y, Cao X-P, Tan L, Tan L (2018) Microglial priming in Alzheimer\u2019s disease. Ann Transl Med. https:\/\/doi.org\/10.21037\/atm.2018.04.22","journal-title":"Ann Transl Med"},{"key":"6004_CR54","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00407","author":"Y Zhao","year":"2017","unstructured":"Zhao Y, Cong L, Lukiw WJ (2017) Lipopolysaccharide (LPS) accumulates in neocortical neurons of Alzheimer\u2019s disease (AD) brain and impairs transcription in human neuronal-glial primary co-cultures. Front Aging Neurosci. https:\/\/doi.org\/10.3389\/fnagi.2017.00407","journal-title":"Front Aging Neurosci"},{"key":"6004_CR55","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1720621","author":"L Xu","year":"2016","unstructured":"Xu L, Pu J (2016) Alpha-synuclein in Parkinson\u2019s disease: from pathogenetic dysfunction to potential clinical application. Parkinsons Dis. https:\/\/doi.org\/10.1155\/2016\/1720621","journal-title":"Parkinsons Dis"},{"key":"6004_CR56","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00370","author":"G Zhang","year":"2018","unstructured":"Zhang G et al (2018) New perspectives on roles of alpha-synuclein in Parkinson\u2019s disease. Front Aging Neurosci. https:\/\/doi.org\/10.3389\/fnagi.2018.00370","journal-title":"Front Aging Neurosci"},{"key":"6004_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2016.10.021","author":"D Ghosh","year":"2017","unstructured":"Ghosh D, Mehra S, Sahay S, Singh PK, Maji SK (2017) \u03b1-synuclein aggregation and its modulation. Int J Biol Macromol. https:\/\/doi.org\/10.1016\/j.ijbiomac.2016.10.021","journal-title":"Int J Biol Macromol"},{"key":"6004_CR58","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a024091","author":"J Burr\u00e9","year":"2018","unstructured":"Burr\u00e9 J, Sharma M, S\u00fcdhof TC (2018) Cell biology and pathophysiology of \u03b1-synuclein. Cold Spring Harb Perspect Med. https:\/\/doi.org\/10.1101\/cshperspect.a024091","journal-title":"Cold Spring Harb Perspect Med"},{"key":"6004_CR59","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.8b00733","author":"D Bhattacharyya","year":"2019","unstructured":"Bhattacharyya D et al (2019) Lipopolysaccharide from gut microbiota modulates \u03b1-synuclein aggregation and alters its biological function. ACS Chem Neurosci. https:\/\/doi.org\/10.1021\/acschemneuro.8b00733","journal-title":"ACS Chem Neurosci"},{"key":"6004_CR60","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00037","author":"CD Rietdijk","year":"2017","unstructured":"Rietdijk CD, Perez-Pardo P, Garssen J, van Wezel RJA, Kraneveld AD (2017) Exploring Braak\u2019s hypothesis of Parkinson\u2019s disease. Front Neurol. https:\/\/doi.org\/10.3389\/fneur.2017.00037","journal-title":"Front Neurol"},{"key":"6004_CR61","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.018","author":"TR Sampson","year":"2016","unstructured":"Sampson TR et al (2016) Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson\u2019s disease. Cell. https:\/\/doi.org\/10.1016\/j.cell.2016.11.018","journal-title":"Cell"},{"key":"6004_CR62","doi-asserted-by":"publisher","DOI":"10.1016\/s0197-4580(02)00065-9","author":"H Braak","year":"2003","unstructured":"Braak H et al (2003) Staging of brain pathology related to sporadic Parkinson\u2019s disease. Neurobiol Aging. https:\/\/doi.org\/10.1016\/s0197-4580(02)00065-9","journal-title":"Neurobiol Aging"},{"key":"6004_CR63","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-022-11491-3","author":"L Soraci","year":"2023","unstructured":"Soraci L et al (2023) Toll-like receptors and NLRP3 inflammasome-dependent pathways in Parkinson\u2019s disease: mechanisms and therapeutic implications. J Neurol. https:\/\/doi.org\/10.1007\/s00415-022-11491-3","journal-title":"J Neurol"},{"key":"6004_CR64","doi-asserted-by":"publisher","unstructured":"He X et al (2020) Ellagic acid produces neuroprotection against LPS-induced dopamine neurotoxicity via the inhibition of microglial NLRP3 inflammasome activation. at https:\/\/doi.org\/10.21203\/rs.2.24392\/v1","DOI":"10.21203\/rs.2.24392\/v1"},{"key":"6004_CR65","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aah4066","author":"R Gordon","year":"2018","unstructured":"Gordon R et al (2018) Inflammasome inhibition prevents \u03b1-synuclein pathology and dopaminergic neurodegeneration in mice. Sci Transl Med. https:\/\/doi.org\/10.1126\/scitranslmed.aah4066","journal-title":"Sci Transl Med"},{"key":"6004_CR66","doi-asserted-by":"publisher","unstructured":"D'Mello C, Swain MG (2017) Immune-to-brain communication pathways in infl ammation-associated sickness and depression. Curr Top Behav Neurosci 31:73\u201394. https:\/\/doi.org\/10.1007\/7854_2016_37","DOI":"10.1007\/7854_2016_37"},{"key":"6004_CR67","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1098","author":"MG Netea","year":"2016","unstructured":"Netea MG et al (2016) Trained immunity: a program of innate immune memory in health and disease. Science. https:\/\/doi.org\/10.1126\/science.aaf1098","journal-title":"Science"},{"key":"6004_CR68","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.07.009","author":"SK Biswas","year":"2009","unstructured":"Biswas SK, Lopez-Collazo E (2009) Endotoxin tolerance: new mechanisms, molecules and clinical significance. Trends Immunol. https:\/\/doi.org\/10.1016\/j.it.2009.07.009","journal-title":"Trends Immunol"},{"key":"6004_CR69","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.0324-18.2018","author":"L Garcia-Bonilla","year":"2018","unstructured":"Garcia-Bonilla L et al (2018) Endogenous protection from ischemic brain injury by preconditioned monocytes. J Neurosci. https:\/\/doi.org\/10.1523\/jneurosci.0324-18.2018","journal-title":"J Neurosci"},{"key":"6004_CR70","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1490-8","author":"O Sheppard","year":"2019","unstructured":"Sheppard O, Coleman MP, Durrant CS (2019) Lipopolysaccharide-induced neuroinflammation induces presynaptic disruption through a direct action on brain tissue involving microglia-derived interleukin 1 beta. J Neuroinflammation. https:\/\/doi.org\/10.1186\/s12974-019-1490-8","journal-title":"J Neuroinflammation"},{"key":"6004_CR71","doi-asserted-by":"publisher","DOI":"10.1186\/s12950-024-00412-y","author":"D Carregosa","year":"2024","unstructured":"Carregosa D et al (2024) Locomotor and gait changes in the LPS model of neuroinflammation are correlated with inflammatory cytokines in blood and brain. J Inflamm. https:\/\/doi.org\/10.1186\/s12950-024-00412-y","journal-title":"J Inflamm"},{"key":"6004_CR72","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00522-2","author":"D Bairamian","year":"2022","unstructured":"Bairamian D et al (2022) Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer\u2019s disease. Mol Neurodegener. https:\/\/doi.org\/10.1186\/s13024-022-00522-2","journal-title":"Mol Neurodegener"},{"key":"6004_CR73","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00444","author":"W Cui","year":"2020","unstructured":"Cui W et al (2020) Inhibition of TLR4 induces M2 microglial polarization and provides neuroprotection via the NLRP3 inflammasome in Alzheimer\u2019s disease. Front Neurosci. https:\/\/doi.org\/10.3389\/fnins.2020.00444","journal-title":"Front Neurosci"},{"key":"6004_CR74","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.068064","author":"N Matsunaga","year":"2011","unstructured":"Matsunaga N, Tsuchimori N, Matsumoto T, Ii M (2011) TAK-242 (resatorvid), a small-molecule inhibitor of Toll-like receptor (TLR) 4 signaling, binds selectively to TLR4 and interferes with interactions between TLR4 and its adaptor molecules. Mol Pharmacol. https:\/\/doi.org\/10.1124\/mol.110.068064","journal-title":"Mol Pharmacol"},{"key":"6004_CR75","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1494114","author":"S Ullah","year":"2025","unstructured":"Ullah S et al (2025) Ambroxol attenuates detrimental effect of LPS-induced glia-mediated neuroinflammation, oxidative stress, and cognitive dysfunction in mice brain. Front Immunol. https:\/\/doi.org\/10.3389\/fimmu.2025.1494114","journal-title":"Front Immunol"},{"key":"6004_CR76","doi-asserted-by":"publisher","first-page":"3833","DOI":"10.1007\/s12035-024-04520-x","volume":"62","author":"S Nigdelioglu Dolanbay","year":"2025","unstructured":"Nigdelioglu Dolanbay S, \u015eirin S, Aslim B (2025) Allocryptopine attenuates inflammatory responses in microglial cells via TLR4-dependent NF-\u03baB and p38 MAPK pathways. Mol Neurobiol 62:3833\u20133847","journal-title":"Mol Neurobiol"},{"key":"6004_CR77","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8071085","author":"NA Cho","year":"2020","unstructured":"Cho NA et al (2020) Impaired hypothalamic microglial activation in offspring of antibiotic-treated pregnant\/lactating rats is attenuated by prebiotic oligofructose co-administration. Microorganisms. https:\/\/doi.org\/10.3390\/microorganisms8071085","journal-title":"Microorganisms"},{"key":"6004_CR78","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.08.029","author":"X Jiang","year":"2016","unstructured":"Jiang X et al (2016) Trans-astaxanthin attenuates lipopolysaccharide-induced neuroinflammation and depressive-like behavior in mice. Brain Res. https:\/\/doi.org\/10.1016\/j.brainres.2016.08.029","journal-title":"Brain Res"},{"key":"6004_CR79","doi-asserted-by":"publisher","DOI":"10.3390\/md17020123","author":"JH Han","year":"2019","unstructured":"Han JH et al (2019) Astaxanthin ameliorates lipopolysaccharide-induced neuroinflammation, oxidative stress and memory dysfunction through inactivation of the signal transducer and activator of transcription 3 pathway. Mar Drugs. https:\/\/doi.org\/10.3390\/md17020123","journal-title":"Mar Drugs"},{"key":"6004_CR80","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2021.10214","author":"Y Zhang","year":"2021","unstructured":"Zhang Y et al (2021) Ginsenoside Rg1 alleviates lipopolysaccharide\u2011induced neuronal damage by inhibiting NLRP1 inflammasomes in HT22 cells. Exp Ther Med. https:\/\/doi.org\/10.3892\/etm.2021.10214","journal-title":"Exp Ther Med"},{"key":"6004_CR81","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01511","author":"BI Arioz","year":"2019","unstructured":"Arioz BI et al (2019) Melatonin attenuates LPS-induced acute depressive-like behaviors and microglial NLRP3 inflammasome activation through the SIRT1\/Nrf2 pathway. Front Immunol. https:\/\/doi.org\/10.3389\/fimmu.2019.01511","journal-title":"Front Immunol"},{"key":"6004_CR82","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1644-8","author":"X Ye","year":"2020","unstructured":"Ye X et al (2020) Lipopolysaccharide induces neuroinflammation in microglia by activating the MTOR pathway and downregulating Vps34 to inhibit autophagosome formation. J Neuroinflammation. https:\/\/doi.org\/10.1186\/s12974-019-1644-8","journal-title":"J Neuroinflammation"},{"key":"6004_CR83","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2025.1546848","author":"J Guo","year":"2025","unstructured":"Guo J, Li Y, Ma K, Su G (2025) Enhancing autophagy mitigates LPS-induced neuroinflammation by inhibiting microglial M1 polarization and neuronophagocytosis. Front Cell Neurosci. https:\/\/doi.org\/10.3389\/fncel.2025.1546848","journal-title":"Front Cell Neurosci"},{"key":"6004_CR84","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01743-1","author":"JS Loh","year":"2024","unstructured":"Loh JS et al (2024) Microbiota\u2013gut\u2013brain axis and its therapeutic applications in neurodegenerative diseases. Sig Transduct Target Ther. https:\/\/doi.org\/10.1038\/s41392-024-01743-1","journal-title":"Sig Transduct Target Ther"},{"key":"6004_CR85","doi-asserted-by":"publisher","unstructured":"Seok J, Warren HS, Cuenca AG et al (2013) Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci USA 110(9):3507\u20133512. https:\/\/doi.org\/10.1073\/pnas.1222878110","DOI":"10.1073\/pnas.1222878110"},{"key":"6004_CR86","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00316","author":"C Vaure","year":"2014","unstructured":"Vaure C, Liu Y (2014) A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front Immunol. https:\/\/doi.org\/10.3389\/fimmu.2014.00316","journal-title":"Front Immunol"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-06004-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-026-06004-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-06004-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T07:38:53Z","timestamp":1781941133000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-026-06004-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":86,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["6004"],"URL":"https:\/\/doi.org\/10.1007\/s12035-026-06004-6","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"18 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 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":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"711"}}