{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Balusu S"],"funding":["European Research Council","Alzheimer's Society"],"pagination":["1176-1182"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7615236"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["381(6663)"],"pubmed_abstract":["Neuronal cell loss is a defining feature of Alzheimer's disease (AD), but the underlying mechanisms remain unclear. We xenografted human or mouse neurons into the brain of a mouse model of AD. Only human neurons displayed tangles, Gallyas silver staining, granulovacuolar neurodegeneration (GVD), phosphorylated tau blood biomarkers, and considerable neuronal cell loss. The long noncoding RNA <i>MEG3</i> was strongly up-regulated in human neurons<i>.</i> This neuron-specific long noncoding RNA is also up-regulated in AD patients. <i>MEG3</i> expression alone was sufficient to induce necroptosis in human neurons in vitro. Down-regulation of <i>MEG3</i> and inhibition of necroptosis using pharmacological or genetic manipulation of receptor-interacting protein kinase 1 (RIPK1), RIPK3, or mixed lineage kinase domain-like protein (MLKL) rescued neuronal cell loss in xenografted human neurons. This model suggests potential therapeutic approaches for AD and reveals a human-specific vulnerability to AD."],"journal":["Science (New York, N.Y.)"],"pubmed_title":["MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer's disease."],"pmcid":["PMC7615236"],"funding_grant_id":["MR/Y014847/1","430","834682","720931","681712","438"],"pubmed_authors":["Balusu S","Salta E","Thal DR","De Strooper B","Simren J","Zetterberg H","Horre K","Chen WT","Fiers M","T'Syen D","Chrysidou I","Arranz AM","Craessaerts K","Sierksma A","Thrupp N","Karikari TK","Snellinx A","Serneels L"],"additional_accession":[]},"is_claimable":false,"name":"MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer's disease.","description":"Neuronal cell loss is a defining feature of Alzheimer's disease (AD), but the underlying mechanisms remain unclear. We xenografted human or mouse neurons into the brain of a mouse model of AD. Only human neurons displayed tangles, Gallyas silver staining, granulovacuolar neurodegeneration (GVD), phosphorylated tau blood biomarkers, and considerable neuronal cell loss. The long noncoding RNA <i>MEG3</i> was strongly up-regulated in human neurons<i>.</i> This neuron-specific long noncoding RNA is also up-regulated in AD patients. <i>MEG3</i> expression alone was sufficient to induce necroptosis in human neurons in vitro. Down-regulation of <i>MEG3</i> and inhibition of necroptosis using pharmacological or genetic manipulation of receptor-interacting protein kinase 1 (RIPK1), RIPK3, or mixed lineage kinase domain-like protein (MLKL) rescued neuronal cell loss in xenografted human neurons. This model suggests potential therapeutic approaches for AD and reveals a human-specific vulnerability to AD.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Sep","modification":"2024-11-20T20:54:29.073Z","creation":"2024-11-20T20:54:29.073Z"},"accession":"S-EPMC7615236","cross_references":{"pubmed":["37708272"],"doi":["10.1126/science.abp9556"]}}