{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:55:12Z","timestamp":1791233712276,"version":"4.1.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"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":["Neurosci. Bull."],"DOI":"10.1007\/s12264-026-01736-w","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:12:32Z","timestamp":1791231152000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RIPK1 Links Metabolic Stresses to Inflammatory and Degenerative Pathways in Alzheimer\u2019s Disease"],"prefix":"10.1007","author":[{"given":"Xiaoshi","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyu","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"1736_CR1","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. Neuroinflammation in Alzheimer\u2019s disease. Lancet Neurol 2015, 14: 388\u2013405.","journal-title":"Lancet Neurol"},{"key":"1736_CR2","doi-asserted-by":"publisher","first-page":"eabm6131","DOI":"10.1126\/science.abm6131","volume":"385","author":"PS Minhas","year":"2024","unstructured":"Minhas PS, Jones JR, Latif-Hernandez A, Sugiura Y, Durairaj AS, Wang Q, et al. Restoring hippocampal glucose metabolism rescues cognition across Alzheimer\u2019s disease pathologies. Science 2024, 385: eabm6131.","journal-title":"Science"},{"key":"1736_CR3","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14556","volume":"21","author":"A Padovani","year":"2025","unstructured":"Padovani A, Galli A, Bazzoli E, Tolassi C, Caratozzolo S, Gumina B, et al. The role of insulin resistance and APOE genotype on blood-brain barrier integrity in Alzheimer\u2019s disease. Alzheimers Dement 2025, 21: e14556.","journal-title":"Alzheimers Dement"},{"key":"1736_CR4","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41583-018-0093-1","volume":"20","author":"J Yuan","year":"2019","unstructured":"Yuan J, Amin P, Ofengeim D. Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases. Nat Rev Neurosci 2019, 20: 19\u201333.","journal-title":"Nat Rev Neurosci"},{"key":"1736_CR5","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/s41422-022-00673-3","volume":"32","author":"W Li","year":"2022","unstructured":"Li W, Shan B, Zou C, Wang H, Zhang MM, Zhu H, et al. Nuclear RIPK1 promotes chromatin remodeling to mediate inflammatory response. Cell Res 2022, 32: 621\u2013637.","journal-title":"Cell Res"},{"key":"1736_CR6","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/nrn3114","volume":"12","author":"BV Zlokovic","year":"2011","unstructured":"Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer\u2019s disease and other disorders. Nat Rev Neurosci 2011, 12: 723\u2013738.","journal-title":"Nat Rev Neurosci"},{"key":"1736_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108447","volume":"33","author":"C Zou","year":"2020","unstructured":"Zou C, Mifflin L, Hu Z, Zhang T, Shan B, Wang H, et al. Reduction of mNAT1\/hNAT2 contributes to cerebral endothelial necroptosis and A\u03b2 accumulation in Alzheimer\u2019s disease. Cell Rep 2020, 33: 108447.","journal-title":"Cell Rep"},{"key":"1736_CR8","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1172\/JCI74692","volume":"125","author":"JW Knowles","year":"2015","unstructured":"Knowles JW, Xie W, Zhang Z, Chennamsetty I, Assimes TL, Paananen J, et al. Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene. J Clin Invest 2015, 125: 1739\u20131751.","journal-title":"J Clin Invest"},{"key":"1736_CR9","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1038\/s41556-024-01540-6","volume":"26","author":"T Zhang","year":"2024","unstructured":"Zhang T, Fu W, Zhang H, Li J, Xing B, Cai Y, et al. Spermidine mediates acetylhypusination of RIPK1 to suppress diabetes onset and progression. Nat Cell Biol 2024, 26: 2099\u20132114.","journal-title":"Nat Cell Biol"},{"key":"1736_CR10","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41583-026-01053-1","volume":"27","author":"S Lewis","year":"2026","unstructured":"Lewis S. Metabolic vulnerability and tau pathology in combination drive necroptosis. Nat Rev Neurosci 2026, 27: 463.","journal-title":"Nat Rev Neurosci"},{"key":"1736_CR11","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1093\/cercor\/bhy078","volume":"29","author":"JN Adams","year":"2019","unstructured":"Adams JN, Lockhart SN, Li L, Jagust WJ. Relationships between tau and glucose metabolism reflect Alzheimer\u2019s disease pathology in cognitively normal older adults. Cereb Cortex 2019, 29: 1997\u20132009.","journal-title":"Cereb Cortex"},{"key":"1736_CR12","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1186\/s12974-022-02567-y","volume":"19","author":"Y Dong","year":"2022","unstructured":"Dong Y, Yu H, Li X, Bian K, Zheng Y, Dai M, et al. Hyperphosphorylated tau mediates neuronal death by inducing necroptosis and inflammation in Alzheimer\u2019s disease. J Neuroinflammation 2022, 19: 205.","journal-title":"J Neuroinflammation"},{"key":"1736_CR13","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s00401-019-02103-y","volume":"139","author":"MJ Koper","year":"2020","unstructured":"Koper MJ, Van Schoor E, Ospitalieri S, Vandenberghe R, Vandenbulcke M, von Arnim CAF, et al. Necrosome complex detected in granulovacuolar degeneration is associated with neuronal loss in Alzheimer\u2019s disease. Acta Neuropathol 2020, 139: 463\u2013484.","journal-title":"Acta Neuropathol"},{"key":"1736_CR14","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1007\/s00401-024-02747-5","volume":"147","author":"S Balusu","year":"2024","unstructured":"Balusu S, De Strooper B. The necroptosis cell death pathway drives neurodegeneration in Alzheimer\u2019s disease. Acta Neuropathol 2024, 147: 96.","journal-title":"Acta Neuropathol"},{"key":"1736_CR15","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s40478-021-01264-w","volume":"9","author":"A Jayaraman","year":"2021","unstructured":"Jayaraman A, Htike TT, James R, Picon C, Reynolds R. TNF-mediated neuroinflammation is linked to neuronal necroptosis in Alzheimer\u2019s disease hippocampus. Acta Neuropathol Commun 2021, 9: 159.","journal-title":"Acta Neuropathol Commun"},{"key":"1736_CR16","doi-asserted-by":"publisher","first-page":"9452","DOI":"10.7150\/thno.62376","volume":"11","author":"C Xu","year":"2021","unstructured":"Xu C, Wu J, Wu Y, Ren Z, Yao Y, Chen G, et al. TNF-\u03b1-dependent neuronal necroptosis regulated in Alzheimer\u2019s disease by coordination of RIPK1-p62 complex with autophagic UVRAG. Theranostics 2021, 11: 9452\u20139469.","journal-title":"Theranostics"},{"key":"1736_CR17","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s40478-022-01332-9","volume":"10","author":"N Salvadores","year":"2022","unstructured":"Salvadores N, Moreno-Gonzalez I, Gamez N, Quiroz G, Vegas-Gomez L, Escand\u00f3n M, et al. A\u03b2 oligomers trigger necroptosis-mediated neurodegeneration via microglia activation in Alzheimer\u2019s disease. Acta Neuropathol Commun 2022, 10: 31.","journal-title":"Acta Neuropathol Commun"},{"key":"1736_CR18","doi-asserted-by":"publisher","first-page":"3205","DOI":"10.1016\/j.neuron.2026.03.035","volume":"114","author":"X Chen","year":"2026","unstructured":"Chen X, Li S, Neubauer A, Li X, Mao W, Brendel M, et al. Glucose hypometabolism and hyperphosphorylated Tau synergistically drive neuronal necroptosis. Neuron 2026, 114: 3205\u20133222.e7.","journal-title":"Neuron"},{"key":"1736_CR19","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","volume":"169","author":"H Keren-Shaul","year":"2017","unstructured":"Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, Ulland TK, et al. A unique microglia type associated with restricting development of Alzheimer\u2019s disease. Cell 2017, 169: 1276\u20131290.e17.","journal-title":"Cell"},{"key":"1736_CR20","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/s41593-019-0566-1","volume":"23","author":"J Marschallinger","year":"2020","unstructured":"Marschallinger J, Iram T, Zardeneta M, Lee SE, Lehallier B, Haney MS, et al. Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain. Nat Neurosci 2020, 23: 194\u2013208.","journal-title":"Nat Neurosci"},{"key":"1736_CR21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2025102118","volume":"118","author":"L Mifflin","year":"2021","unstructured":"Mifflin L, Hu Z, Dufort C, Hession CC, Walker AJ, Niu K, et al. A RIPK1-regulated inflammatory microglial state in amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 2021, 118: e2025102118.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1736_CR22","doi-asserted-by":"publisher","first-page":"E8788","DOI":"10.1073\/pnas.1714175114","volume":"114","author":"D Ofengeim","year":"2017","unstructured":"Ofengeim D, Mazzitelli S, Ito Y, DeWitt JP, Mifflin L, Zou C, et al. RIPK1 mediates a disease-associated microglial response in Alzheimer\u2019s disease. Proc Natl Acad Sci U S A 2017, 114: E8788\u2013E8797.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1736_CR23","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.immuni.2026.01.014","volume":"59","author":"X Xie","year":"2026","unstructured":"Xie X, Liu J, Liang W, Zhang Y, Gong X, Yuan S, et al. Repression of RIPK1 kinase by INPP5D inhibits expression of diverse proinflammatory mediators and late-onset Alzheimer\u2019s disease risk factors. Immunity 2026, 59: 419\u2013437.e11.","journal-title":"Immunity"},{"key":"1736_CR24","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/s41573-020-0071-y","volume":"19","author":"L Mifflin","year":"2020","unstructured":"Mifflin L, Ofengeim D, Yuan J. Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target. Nat Rev Drug Discov 2020, 19: 553\u2013571.","journal-title":"Nat Rev Drug Discov"},{"key":"1736_CR25","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1002\/cpt.1615","volume":"107","author":"HW Grievink","year":"2020","unstructured":"Grievink HW, Heuberger JAAC, Huang F, Chaudhary R, Birkhoff WAJ, Tonn GR, et al. DNL104, a centrally penetrant RIPK1 inhibitor, inhibits RIP1 kinase phosphorylation in a randomized phase I ascending dose study in healthy volunteers. Clin Pharmacol Ther 2020, 107: 406\u2013414.","journal-title":"Clin Pharmacol Ther"},{"key":"1736_CR26","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1111\/cts.13317","volume":"15","author":"MFJM Vissers","year":"2022","unstructured":"Vissers MFJM, Heuberger JAAC, Groeneveld GJ, Oude Nijhuis J, De Deyn PP, Hadi S, et al. Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: Randomized, placebo-controlled, double-blind phase I\/Ib studies in healthy subjects and patients. Clin Transl Sci 2022, 15: 2010\u20132023.","journal-title":"Clin Transl Sci"},{"key":"1736_CR27","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/s13075-021-02468-0","volume":"23","author":"K Weisel","year":"2021","unstructured":"Weisel K, Berger S, Thorn K, Taylor PC, Peterfy C, Siddall H, et al. A randomized, placebo-controlled experimental medicine study of RIPK1 inhibitor GSK2982772 in patients with moderate to severe rheumatoid arthritis. Arthritis Res Ther 2021, 23: 85.","journal-title":"Arthritis Res Ther"},{"key":"1736_CR28","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgast-2021-000680","volume":"8","author":"K Weisel","year":"2021","unstructured":"Weisel K, Scott N, Berger S, Wang S, Brown K, Powell M, et al. A randomised, placebo-controlled study of RIPK1 inhibitor GSK2982772 in patients with active ulcerative colitis. BMJ Open Gastroenterol 2021, 8: e000680.","journal-title":"BMJ Open Gastroenterol"},{"key":"1736_CR29","doi-asserted-by":"publisher","first-page":"1642593","DOI":"10.3389\/fimmu.2025.1642593","volume":"16","author":"A Pajulas","year":"2025","unstructured":"Pajulas A, Sims JT, Hanson EP, Vendel AC. RIPK1 signaling pathways: Implications for autoimmune and neuroinflammatory diseases. Front Immunol 2025, 16: 1642593.","journal-title":"Front Immunol"}],"container-title":["Neuroscience Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12264-026-01736-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12264-026-01736-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12264-026-01736-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:12:33Z","timestamp":1791231153000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12264-026-01736-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":29,"alternative-id":["1736"],"URL":"https:\/\/doi.org\/10.1007\/s12264-026-01736-w","relation":{},"ISSN":["1673-7067","1995-8218"],"issn-type":[{"value":"1673-7067","type":"print"},{"value":"1995-8218","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"assertion":[{"value":"12 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Ethics"}}]}}