{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kumar S"],"funding":["NIH-NIA","Alzheimer’s Association","NIH-NINDS","NIA NIH HHS","University of Virginia Brain Institute","NINDS NIH HHS","Owens Family Foundation","NIH HHS","Commonwealth of Virginia"],"pagination":["e157433"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9977425"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(3)"],"pubmed_abstract":["The molecular mediators of cell death and inflammation in Alzheimer's disease (AD) have yet to be fully elucidated. Caspase-8 is a critical regulator of several cell death and inflammatory pathways; however, its role in AD pathogenesis has not yet been examined in detail. In the absence of caspase-8, mice are embryonic lethal due to excessive receptor interacting protein kinase 3-dependent (RIPK3-dependent) necroptosis. Compound RIPK3 and caspase-8 mutants rescue embryonic lethality, which we leveraged to examine the roles of these pathways in an amyloid β-mediated (Aβ-mediated) mouse model of AD. We found that combined deletion of caspase-8 and RIPK3, but not RIPK3 alone, led to diminished Aβ deposition and microgliosis in the mouse model of AD carrying human presenilin 1 and amyloid prec"],"journal":["JCI insight"],"pubmed_title":["Role of the caspase-8/RIPK3 axis in Alzheimer's disease pathogenesis and Aβ-induced NLRP3 inflammasome activation."],"pmcid":["PMC9977425"],"funding_grant_id":["Related Diseases Research Award Fund","NA","Presidential Neuroscience Graduate Fellowship","AARG-18-566113","1RF1AG071996-01","R01NS091617,R01NS106383","R01 NS106383","S10 OD025156","R01 NS091617","Alzheimer’s","RF1 AG071996"],"pubmed_authors":["Lukens JR","Oliveira CB","Kahle AD","Deppmann CD","Budhathoki S","Calhan OY","Kumar S"],"additional_accession":[]},"is_claimable":false,"name":"Role of the caspase-8/RIPK3 axis in Alzheimer's disease pathogenesis and Aβ-induced NLRP3 inflammasome activation.","description":"The molecular mediators of cell death and inflammation in Alzheimer's disease (AD) have yet to be fully elucidated. Caspase-8 is a critical regulator of several cell death and inflammatory pathways; however, its role in AD pathogenesis has not yet been examined in detail. In the absence of caspase-8, mice are embryonic lethal due to excessive receptor interacting protein kinase 3-dependent (RIPK3-dependent) necroptosis. Compound RIPK3 and caspase-8 mutants rescue embryonic lethality, which we leveraged to examine the roles of these pathways in an amyloid β-mediated (Aβ-mediated) mouse model of AD. We found that combined deletion of caspase-8 and RIPK3, but not RIPK3 alone, led to diminished Aβ deposition and microgliosis in the mouse model of AD carrying human presenilin 1 and amyloid prec","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2026-05-28T08:09:15.04Z","creation":"2025-04-25T16:55:35.536Z"},"accession":"S-EPMC9977425","cross_references":{"pubmed":["36602874"],"doi":["10.1172/jci.insight.157433"]}}