{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pandey S"],"funding":["NCI NIH HHS"],"pagination":["102336"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11905928"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(12)"],"pubmed_abstract":["Small molecules that can reduce the neurotoxic beta-amyloid (Aβ) aggregates in the brain provide a potential treatment for Alzheimer disease (AD). Most screening methods for small-molecule hits focus on the overall Aβ aggregations without a specific target, such as the very first association step (i.e., nucleation) <i>en route</i> to the Aβ oligomers. Located in the middle of a full-length Aβ peptide, Aβ<sub>19-20</sub> (diphenylalanine or FF) nucleates the neurotoxic Aβ oligomer formation. Here, we innovate a single-molecule screen method in optical tweezers by targeting the nucleation process in Aβ aggregation, namely FF-dimerization. With a 121-compound National Institutes of Health (NIH) library, we identify 12 inhibitors and 8 stimulants that can inhibit/promote Aβ<sub>19-20</sub> dim"],"journal":["Cell reports. Physical science"],"pubmed_title":["&lt;i&gt;De novo&lt;/i&gt; design of a mechano-pharmaceutical screening platform against formation of individual beta-amyloid oligomers."],"pmcid":["PMC11905928"],"funding_grant_id":["R01 CA252827"],"pubmed_authors":["Zhang G","Pokhrel P","Harris P","Sharma G","Mao H","Hao Y","Jeon BT","Pandey S","Christensen NJ","Zhang Z","Danielsen MB","Lou C","Leng Y","Xiang Y","Song S","Sorensen KK","Kim MH","Cunningham R"],"additional_accession":[]},"is_claimable":false,"name":"&lt;i&gt;De novo&lt;/i&gt; design of a mechano-pharmaceutical screening platform against formation of individual beta-amyloid oligomers.","description":"Small molecules that can reduce the neurotoxic beta-amyloid (Aβ) aggregates in the brain provide a potential treatment for Alzheimer disease (AD). Most screening methods for small-molecule hits focus on the overall Aβ aggregations without a specific target, such as the very first association step (i.e., nucleation) <i>en route</i> to the Aβ oligomers. Located in the middle of a full-length Aβ peptide, Aβ<sub>19-20</sub> (diphenylalanine or FF) nucleates the neurotoxic Aβ oligomer formation. Here, we innovate a single-molecule screen method in optical tweezers by targeting the nucleation process in Aβ aggregation, namely FF-dimerization. With a 121-compound National Institutes of Health (NIH) library, we identify 12 inhibitors and 8 stimulants that can inhibit/promote Aβ<sub>19-20</sub> dim","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2025-04-26T03:23:41.458Z","creation":"2025-04-06T10:51:16.939Z"},"accession":"S-EPMC11905928","cross_references":{"pubmed":["40083584"],"doi":["10.1016/j.xcrp.2024.102336"]}}