{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["1"],"submitter":["Cui J"],"pubmed_abstract":["Despite decades of intense global effort, no disease-modifying drugs for Alzheimer's disease have emerged. Molecules targeting catalytic activities of γ-secretase or β-site APP-cleaving enzyme 1 (BACE1) have been beset by undesired side effects. We hypothesized that blocking the interaction between BACE1 and γ-secretase subunit presenilin-1 (PS1) might offer an alternative strategy to selectively suppress Aβ generation. Through high-throughput screening, we discovered that 3-α-akebonoic acid (3AA) interferes with PS1/BACE1 interaction and reduces Aβ production. Structural analogs of 3AA were systematically synthesized and the functional analog XYT472B was identified. Photo-activated crosslinking and biochemical competition assays showed that 3AA and XYT472B bind to PS1, interfere with PS1/"],"journal":["Cell discovery"],"pagination":["15021"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4860824"],"repository":["biostudies-literature"],"pubmed_title":["Targeting the γ-/β-secretase interaction reduces β-amyloid generation and ameliorates Alzheimer's disease-related pathogenesis."],"pmcid":["PMC4860824"],"pubmed_authors":["Li W","Li X","Gu H","Xie X","Zhang Y","Cui J","Nan F","Wang X","Zhang C","Zhao J","Pei G"],"additional_accession":[]},"is_claimable":false,"name":"Targeting the γ-/β-secretase interaction reduces β-amyloid generation and ameliorates Alzheimer's disease-related pathogenesis.","description":"Despite decades of intense global effort, no disease-modifying drugs for Alzheimer's disease have emerged. Molecules targeting catalytic activities of γ-secretase or β-site APP-cleaving enzyme 1 (BACE1) have been beset by undesired side effects. We hypothesized that blocking the interaction between BACE1 and γ-secretase subunit presenilin-1 (PS1) might offer an alternative strategy to selectively suppress Aβ generation. Through high-throughput screening, we discovered that 3-α-akebonoic acid (3AA) interferes with PS1/BACE1 interaction and reduces Aβ production. Structural analogs of 3AA were systematically synthesized and the functional analog XYT472B was identified. Photo-activated crosslinking and biochemical competition assays showed that 3AA and XYT472B bind to PS1, interfere with PS1/","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015","modification":"2025-04-19T23:19:27.235Z","creation":"2019-03-27T02:13:18Z"},"accession":"S-EPMC4860824","cross_references":{"pubmed":["27462420"],"doi":["10.1038/celldisc.2015.21"]}}