{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["11(22)"],"submitter":["Sanchez-Garcia MA"],"pubmed_abstract":["Microglia respond to Alzheimer's disease (AD) with varied transcriptional responses. We show that oligomeric Aß (oAß) induces the expression of <i>Hif1a</i> and <i>Egln3</i> in microglia in vitro, together with the transcription of the type I interferon signature (IFNS) genes in a PHD3-dependent manner. We identify FOXO3 as a repressor of IFNS, whose abundance decreases upon PHD3 induction in response to oAß. In vivo, loss of PHD3 correlates with abrogation of the IFNS and activation of the disease-associated microglia signature, an increase in microglia proximity to Aß plaques and phagocytosis of both Aß and small plaques. PHD3 deficiency mitigated the Aß plaque-associated neuropathology and rescued behavioral deficits of an AD mouse model. Last, we demonstrate that microglial PHD3 overex"],"journal":["Science advances"],"pagination":["eadu2244"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12118632"],"repository":["biostudies-literature"],"pubmed_title":["Inactivation of the PHD3-FOXO3 axis blunts the type I interferon response in microglia and ameliorates Alzheimer's disease progression."],"pmcid":["PMC12118632"],"pubmed_authors":["Barba-Reyes JM","Munoz-Manchado AB","Rosales-Nieves AE","Ortega-de San Luis C","Munoz-Cabello AM","Lopez-Barneo J","Vizuete M","March-Diaz R","Heras-Garvin A","Navarro V","Mora-Romero B","Sanchez-Garcia MA","Romero-Molina C","Quinones-Canete S","Pascual A","Cokman ME","Vitorica J","Lara-Urena N","Cabello-Rivera D"],"additional_accession":[]},"is_claimable":false,"name":"Inactivation of the PHD3-FOXO3 axis blunts the type I interferon response in microglia and ameliorates Alzheimer's disease progression.","description":"Microglia respond to Alzheimer's disease (AD) with varied transcriptional responses. We show that oligomeric Aß (oAß) induces the expression of <i>Hif1a</i> and <i>Egln3</i> in microglia in vitro, together with the transcription of the type I interferon signature (IFNS) genes in a PHD3-dependent manner. We identify FOXO3 as a repressor of IFNS, whose abundance decreases upon PHD3 induction in response to oAß. In vivo, loss of PHD3 correlates with abrogation of the IFNS and activation of the disease-associated microglia signature, an increase in microglia proximity to Aß plaques and phagocytosis of both Aß and small plaques. PHD3 deficiency mitigated the Aß plaque-associated neuropathology and rescued behavioral deficits of an AD mouse model. Last, we demonstrate that microglial PHD3 overex","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 May","modification":"2026-06-02T20:33:56.287Z","creation":"2026-05-27T03:07:58.38Z"},"accession":"S-EPMC12118632","cross_references":{"pubmed":["40435260"],"doi":["10.1126/sciadv.adu2244"]}}