{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["114(6)"],"submitter":["Mansilla A"],"pubmed_abstract":["The protein complex formed by the Ca<sup>2+</sup> sensor neuronal calcium sensor 1 (NCS-1) and the guanine exchange factor protein Ric8a coregulates synapse number and probability of neurotransmitter release, emerging as a potential therapeutic target for diseases affecting synapses, such as fragile X syndrome (FXS), the most common heritable autism disorder. Using crystallographic data and the virtual screening of a chemical library, we identified a set of heterocyclic small molecules as potential inhibitors of the NCS-1/Ric8a interaction. The aminophenothiazine FD44 interferes with NCS-1/Ric8a binding, and it restores normal synapse number and associative learning in a Drosophila FXS model. The synaptic effects elicited by FD44 feeding are consistent with the genetic manipulation of NCS-"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pagination":["E999-E1008"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5307446"],"repository":["biostudies-literature"],"pubmed_title":["Interference of the complex between NCS-1 and Ric8a with phenothiazines regulates synaptic function and is an approach for fragile X syndrome."],"pmcid":["PMC5307446"],"pubmed_authors":["Sanchez-Barrena MJ","Campillo NE","Gonzalez-Rubio JM","Semelidou O","Ferrus A","Infantes L","Gil C","Martinez-Gonzalez L","Mansilla A","Martinez A","Skoulakis EM","Chaves-Sanjuan A","Conde S"],"additional_accession":[]},"is_claimable":false,"name":"Interference of the complex between NCS-1 and Ric8a with phenothiazines regulates synaptic function and is an approach for fragile X syndrome.","description":"The protein complex formed by the Ca<sup>2+</sup> sensor neuronal calcium sensor 1 (NCS-1) and the guanine exchange factor protein Ric8a coregulates synapse number and probability of neurotransmitter release, emerging as a potential therapeutic target for diseases affecting synapses, such as fragile X syndrome (FXS), the most common heritable autism disorder. Using crystallographic data and the virtual screening of a chemical library, we identified a set of heterocyclic small molecules as potential inhibitors of the NCS-1/Ric8a interaction. The aminophenothiazine FD44 interferes with NCS-1/Ric8a binding, and it restores normal synapse number and associative learning in a Drosophila FXS model. The synaptic effects elicited by FD44 feeding are consistent with the genetic manipulation of NCS-","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Feb","modification":"2025-04-05T09:35:15.315Z","creation":"2019-03-27T02:36:25Z"},"accession":"S-EPMC5307446","cross_references":{"pubmed":["28119500"],"doi":["10.1073/pnas.1611089114"]}}