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PXD036283-1

PXD036283 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRepurposing of Amisulpride, a known antipsychotic drug, to target synovial fibroblasts activation in arthritis.
DescriptionSynovial Fibroblasts (SFs) are key pathogenic drivers in arthritis and their in vivo activation by TNF is sufficient to orchestrate full arthritic pathogenesis in animal models. TNF blockade has been efficacious for a large percentage of Rheumatoid Arthritis (RA) patients, although characterized by a plethora of side effects. Novel therapeutic discoveries remain however challenging, especially in optimizing drug safety, side effects, longer-term responses, costs and administration routes. Aiming to find new potent therapeutics, we applied the L1000CDS2 search engine, in order to identify compounds that could potentially reverse the pathogenic expression signature of arthritogenic SFs, derived from the human TNF transgenic mouse model (hTNFtg). We identified a neuroleptic drug, namely Amisulpride, which was validated to reduce SFs’ inflammatory potential while decreasing the clinical score of hTNFtg polyarthritis. Notably, we found that Amisulpride did not exert its biological activities through its known targets Dopamine receptors 2 and 3 and Serotonin Receptor 7, nor through TNFTNFRI binding inhibition. By applying a click chemistry approach, novel potential targets of Amisulpride were identified, which were further validated to repress hTNFtg SFs’ inflammatory potential in vitro (Ascc3 and Sec62), while phosphoproteomics analysis revealed important fibroblast activation pathways, such as adhesion, to be altered upon treatment. Our data support that Amisulpride could provide an additive beneficial effect to patients suffering from RA and comorbid dysthymia, as it may reduce SFs pathogenicity in parallel with its antidepressive activity. Importantly, Amisulpride may also serve as a “lead” compound for the development of novel, more potent therapeutics against chronic inflammatory diseases
HostingRepositoryPRIDE
AnnounceDate2023-04-06
AnnouncementXMLSubmission_2023-04-06_06:09:01.983.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMartinaSamiotaki
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-08-25 13:50:02ID requested
12023-04-06 06:09:02announced
22023-11-14 08:58:04announced2023-11-14: Updated project metadata.
Publication List
Keyword List
submitter keyword: Rheumatoid arthritis,Amisulpride, Repurposing, synovial fibroblasts, Chemical Proteomics, Click-Chemistry
Contact List
GeorgeKollias
contact affiliationInstitute for Bioinnovation, Biomedical Sciences Research Centre (B.S.R.C.) “Alexander Fleming”; Vari, Greece
contact emailkollias@fleming.gr
lab head
MartinaSamiotaki
contact affiliationProtein Analysis Laboratory B.S.R.C. "Alexander Fleming", Alexander Fleming Street 34 16672, Vari, Greece
contact emailsamiotaki@fleming.gr
dataset submitter
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