{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["116(25)"],"submitter":["Bahn G"],"pubmed_abstract":["BACE1 is the rate-limiting enzyme for amyloid-β peptides (Aβ) generation, a key event in the pathogenesis of Alzheimer's disease (AD). By an unknown mechanism, levels of <i>BACE1</i> and a <i>BACE1</i> mRNA-stabilizing antisense RNA (<i>BACE1-AS</i>) are elevated in the brains of AD patients, implicating that dysregulation of <i>BACE1</i> expression plays an important role in AD pathogenesis. We found that nuclear factor erythroid-derived 2-related factor 2 (NRF2/NFE2L2) represses the expression of <i>BACE1</i> and <i>BACE1-AS</i> through binding to antioxidant response elements (AREs) in their promoters of mouse and human. NRF2-mediated inhibition of <i>BACE1</i> and <i>BACE1-AS</i> expression is independent of redox regulation. NRF2 activation decreases production of <i>BACE1</i> and <i>BACE1-AS</i> transcripts and Aβ production and ameliorates cognitive deficits in animal models of AD. Depletion of NRF2 increases <i>BACE1</i> and <i>BACE1-AS</i> expression and Aβ production and worsens cognitive deficits. Our findings suggest that activation of NRF2 can prevent a key early pathogenic process in AD."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pagination":["12516-12523"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6589670"],"repository":["biostudies-literature"],"pubmed_title":["NRF2/ARE pathway negatively regulates BACE1 expression and ameliorates cognitive deficits in mouse Alzheimer's models."],"pmcid":["PMC6589670"],"pubmed_authors":["Yun UJ","Kim HK","Mattson MP","Bae SH","Arumugam TV","Bahn G","Lee YJ","Baik SH","Park JS","Sul JH","Baek SH","Cho YS","Wakabayashi N","Choi Y","Lim J","Han J","Jo DG","Choi BY","Han JW"],"additional_accession":[]},"is_claimable":false,"name":"NRF2/ARE pathway negatively regulates BACE1 expression and ameliorates cognitive deficits in mouse Alzheimer's models.","description":"BACE1 is the rate-limiting enzyme for amyloid-β peptides (Aβ) generation, a key event in the pathogenesis of Alzheimer's disease (AD). By an unknown mechanism, levels of <i>BACE1</i> and a <i>BACE1</i> mRNA-stabilizing antisense RNA (<i>BACE1-AS</i>) are elevated in the brains of AD patients, implicating that dysregulation of <i>BACE1</i> expression plays an important role in AD pathogenesis. We found that nuclear factor erythroid-derived 2-related factor 2 (NRF2/NFE2L2) represses the expression of <i>BACE1</i> and <i>BACE1-AS</i> through binding to antioxidant response elements (AREs) in their promoters of mouse and human. NRF2-mediated inhibition of <i>BACE1</i> and <i>BACE1-AS</i> expression is independent of redox regulation. NRF2 activation decreases production of <i>BACE1</i> and <i>BACE1-AS</i> transcripts and Aβ production and ameliorates cognitive deficits in animal models of AD. Depletion of NRF2 increases <i>BACE1</i> and <i>BACE1-AS</i> expression and Aβ production and worsens cognitive deficits. Our findings suggest that activation of NRF2 can prevent a key early pathogenic process in AD.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jun","modification":"2025-04-22T00:29:07.018Z","creation":"2025-04-05T19:33:57.931Z"},"accession":"S-EPMC6589670","cross_references":{"pubmed":["31164420"],"doi":["10.1073/pnas.1819541116"]}}