{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T14:31:30Z","timestamp":1793025090703,"version":"4.5.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>JOURNAL\/nrgr\/04.03\/01300535-202507000-00028\/figure1\/v\/2026-04-26T112544Z\/r\/image-tiff<\/jats:p>\n                  <jats:p>\n                    Alzheimer\u2019s disease is characterized by deposition of amyloid-\u03b2, which forms extracellular neuritic plaques, and accumulation of hyperphosphorylated tau, which aggregates to form intraneuronal neurofibrillary tangles, in the brain. The NLRP3 inflammasome may play a role in the transition from amyloid-\u03b2 deposition to tau phosphorylation and aggregation. Because NLRP3 is primarily found in brain microglia, and tau is predominantly located in neurons, it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines. Here, we found that neurons also express NLRP3\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    , and that neuronal NLRP3 regulates tau phosphorylation. Using biochemical methods, we mapped the minimal\n                    <jats:italic toggle=\"yes\">NLRP3<\/jats:italic>\n                    promoter and identified FUBP3 as a transcription factor regulating\n                    <jats:italic toggle=\"yes\">NLRP3<\/jats:italic>\n                    expression in neurons. In primary neurons and the neuroblastoma cell line Neuro2A, FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-\u03b2 is present. In the brains of aged wild-type mice and a mouse model of Alzheimer\u2019s disease, FUBP3 expression was markedly increased in cortical neurons. Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses. We also found that FUBP3 trimmed the 5\u2032 end of DNA fragments that it bound, implying that FUBP3 functions in stress-induced responses. These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-\u03b2-to\u2013phospho-tau transition than microglial NLRP3, and that amyloid-\u03b2 fundamentally alters the regulatory mechanism of\n                    <jats:italic toggle=\"yes\">NLRP3<\/jats:italic>\n                    expression in neurons. Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer\u2019s disease mice, FUBP3 could be a safe therapeutic target for preventing Alzheimer\u2019s disease progression.\n                  <\/jats:p>","DOI":"10.4103\/nrr.nrr-d-23-01799","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T12:00:29Z","timestamp":1715342429000},"page":"2068-2083","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["FUBP3 mediates the amyloid-\u03b2-induced neuronal NLRP3 expression"],"prefix":"10.4103","volume":"20","author":[{"given":"Jing","family":"Yao","sequence":"first","affiliation":[{"name":"The National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"The National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenping","family":"Liang","sequence":"additional","affiliation":[{"name":"The National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"The National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4255-6763","authenticated-orcid":false,"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[{"name":"The National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Song","sequence":"additional","affiliation":[{"name":"The National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China"},{"name":"Department of Pediatrics, The Second Affiliated Hospital and Yuying Children\u2019s Hospital, Key Laboratory of Alzheimer\u2019s Disease of Zhejiang Province, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang Province, China"},{"name":"Oujiang Laboratory (Zhejiang Laboratory for Regenerative Medicine, Vision, and Brain Health), Wenzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"R1-20260426","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s12974-023-02830-w","article-title":"Pharmacologic inhibition of NLRP3 reduces the levels of \u03b1-synuclein and protects dopaminergic neurons in a model of Parkinson\u2019s disease","volume":"20","author":"Amo-Aparicio","year":"2023","journal-title":"J Neuroinflammation"},{"key":"R2-20260426","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.bbi.2023.09.011","article-title":"P2X(7)R influences tau aggregate burden in human tauopathies and shows distinct signalling in microglia and 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Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/NRR.NRR-D-23-01799","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T18:53:53Z","timestamp":1786647233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/NRR.NRR-D-23-01799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,13]]},"references-count":51,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/nrr.nrr-d-23-01799","relation":{},"ISSN":["1673-5374","1876-7958"],"issn-type":[{"value":"1673-5374","type":"print"},{"value":"1876-7958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,13]]},"assertion":[{"value":"2023-11-01","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-13","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}