{"doi":"10.1016/j.bbadis.2021.166152","title":"Oxidative modification impairs SERCA activity in Drosophila and human cell models of Parkinson's disease","abstract":"DJ-1 is a causative gene for familial Parkinson's disease (PD) with different functions, standing out its role against oxidative stress (OS). Accordingly, PD model flies harboring a mutation in the DJ-1β gene (the Drosophila ortholog of human DJ-1) show high levels of OS markers like protein carbonylation, a common post-translational modification that may alter protein function. To increase our understanding of PD pathogenesis as well as to discover potential therapeutic targets for pharmacological intervention, we performed a redox proteomic assay in DJ-1β mutant flies. Among the proteins that showed increased carbonylation levels in PD model flies, we found SERCA, an endoplasmic reticulum Ca2+ channel that plays an important role in Ca2+ homeostasis. Interestingly, several studies have supported the involvement of Ca2+ dyshomeostasis in PD. Thus, we decided to study the relation between SERCA activity and PD physiopathology. Our results showed that SERCA enzymatic activity is significantly reduced in DJ-1β mutant flies, probably as a consequence of OS-induced carbonylation, as well as in a human cell PD model based on DJ-1-deficiency. Indeed, higher carbonylation levels of SERCA were also observed in DJ-1-deficient cells compared to controls. In addition, the specific activator of SERCA, CDN1163, was also able to restore PD-related phenotypes in both familial PD models by increasing SERCA activity. Taken together, our results indicate that impaired SERCA activity due to oxidative modification may play a role in PD physiopathology. Furthermore, we demonstrate that therapeutic strategies addressing SERCA activation could be beneficial to treat this disease as shown for CDN1163.","journal":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease","year":2021,"id":171581,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":706368,"name":"Verónica Francisca Loewe Muñoz","orcid":"0000-0003-4482-0214","position":1,"is_corresponding":false},{"id":706369,"name":"F. Sanz","orcid":"0000-0002-2532-0487","position":2,"is_corresponding":false},{"id":706370,"name":"Nuria Paricio","orcid":"0000-0001-7193-2532","position":3,"is_corresponding":false},{"id":706367,"name":"Cristina Solana‐Manrique","orcid":"0000-0001-5148-8796","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T23:46:33.067299Z","pmid":"33892078","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}