{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bomfim TR"],"funding":["NIA NIH HHS","CIHR"],"pagination":["1339-53"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3314445"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["122(4)"],"pubmed_abstract":["Defective brain insulin signaling has been suggested to contribute to the cognitive deficits in patients with Alzheimer's disease (AD). Although a connection between AD and diabetes has been suggested, a major unknown is the mechanism(s) by which insulin resistance in the brain arises in individuals with AD. Here, we show that serine phosphorylation of IRS-1 (IRS-1pSer) is common to both diseases. Brain tissue from humans with AD had elevated levels of IRS-1pSer and activated JNK, analogous to what occurs in peripheral tissue in patients with diabetes. We found that amyloid-β peptide (Aβ) oligomers, synaptotoxins that accumulate in the brains of AD patients, activated the JNK/TNF-α pathway, induced IRS-1 phosphorylation at multiple serine residues, and inhibited physiological IRS-1pTyr in "],"journal":["The Journal of clinical investigation"],"pubmed_title":["An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease- associated Aβ oligomers."],"pmcid":["PMC3314445"],"funding_grant_id":["90396","R01-AG22547","R01 AG018877","MOP-77734","R01 AG022547","R01-AG18877"],"pubmed_authors":["Klein WL","Bomfim TR","Sathler LB","Kazi H","Forny-Germano L","Munoz DP","McClean PL","Brito-Moreira J","Houzel JC","Talbot K","De Felice FG","Silverman MA","Melo HM","Arnold SE","Decker H","Ferreira ST","Holscher C"],"additional_accession":[]},"is_claimable":false,"name":"An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease- associated Aβ oligomers.","description":"Defective brain insulin signaling has been suggested to contribute to the cognitive deficits in patients with Alzheimer's disease (AD). Although a connection between AD and diabetes has been suggested, a major unknown is the mechanism(s) by which insulin resistance in the brain arises in individuals with AD. Here, we show that serine phosphorylation of IRS-1 (IRS-1pSer) is common to both diseases. Brain tissue from humans with AD had elevated levels of IRS-1pSer and activated JNK, analogous to what occurs in peripheral tissue in patients with diabetes. We found that amyloid-β peptide (Aβ) oligomers, synaptotoxins that accumulate in the brains of AD patients, activated the JNK/TNF-α pathway, induced IRS-1 phosphorylation at multiple serine residues, and inhibited physiological IRS-1pTyr in ","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Apr","modification":"2025-04-05T15:41:59.346Z","creation":"2019-03-27T00:51:40Z"},"accession":"S-EPMC3314445","cross_references":{"pubmed":["22476196"],"doi":["10.1172/jci57256","10.1172/JCI57256"]}}