{"doi":"10.1111/cns.70109","title":"Targeting Myeloperoxidase to Reduce Neuroinflammation in X‐Linked Dystonia Parkinsonism","abstract":"AIMS: Although the genetic locus of X-linked dystonia parkinsonism (XDP), a neurodegenerative disease endemic in the Philippines, is well-characterized, the exact mechanisms leading to neuronal loss are not yet fully understood. Recently, we demonstrated an increase in myeloperoxidase (MPO) levels in XDP postmortem prefrontal cortex (PFC), suggesting a role for inflammation in XDP pathogenesis. Therefore, we hypothesized that inhibiting MPO could provide a therapeutic strategy for XDP. METHODS: MPO activity was measured by using an MPO-activatable fluorescent agent (MAFA) in human postmortem PFC. Reactive oxygen species (ROS) and MPO activity were measured in XDP-derived fibroblasts and SH-SY5Y cells following MPO inhibition. RESULTS: MPO activity was significantly increased in XDP PFC. Additionally, treatment of cell lines with postmortem XDP PFC resulted in a significant increase in ROS levels. To determine whether increases in MPO activity caused increases in ROS, MPO content was immunodepleted from XDP PFC, which resulted in a significant decrease in ROS in SH-SY5Y cells. Consistently, the treatment with verdiperstat, a potent and selective MPO inhibitor, significantly decreased ROS in both XDP-derived fibroblasts and XDP PFC-treated SH-SY5Y cells. CONCLUSIONS: Collectively, our results suggest that MPO inhibition mitigates oxidative stress and may provide a novel therapeutic strategy for XDP treatment.","journal":"CNS Neuroscience & Therapeutics","year":2024,"id":458705,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":792191,"name":"Negin Jalali Motlagh","orcid":"0000-0002-1739-4320","position":1,"is_corresponding":false},{"id":1285488,"name":"Ranee Zara B. Monsanto","orcid":null,"position":2,"is_corresponding":false},{"id":895104,"name":"Dan Lei","orcid":"0000-0001-6944-1873","position":3,"is_corresponding":false},{"id":1284971,"name":"Micaela G. Murcar","orcid":"0000-0003-3050-7964","position":4,"is_corresponding":false},{"id":425519,"name":"Ellen B. Penney","orcid":null,"position":5,"is_corresponding":false},{"id":441305,"name":"D. Cristopher Bragg","orcid":"0000-0003-3203-6262","position":6,"is_corresponding":false},{"id":1285489,"name":"Cara Fernandez‐Cerado","orcid":null,"position":7,"is_corresponding":false},{"id":1285490,"name":"G. Paul Legarda","orcid":null,"position":8,"is_corresponding":false},{"id":1284972,"name":"Michelle Sy","orcid":"0000-0001-7130-7569","position":9,"is_corresponding":false},{"id":1285491,"name":"Edwin L. Muñoz","orcid":null,"position":10,"is_corresponding":false},{"id":1284973,"name":"Mark C. Ang","orcid":"0000-0003-1292-9493","position":11,"is_corresponding":false},{"id":1284974,"name":"Cid Czarina E. Diesta","orcid":"0000-0003-3068-1065","position":12,"is_corresponding":false},{"id":638857,"name":"Can Zhang","orcid":"0000-0003-3529-5438","position":13,"is_corresponding":false},{"id":226532,"name":"Rudolph E. Tanzi","orcid":"0000-0002-7032-1454","position":14,"is_corresponding":false},{"id":743692,"name":"Irfan Qureshi","orcid":"0000-0002-0572-0993","position":15,"is_corresponding":false},{"id":580534,"name":"John W. Chen","orcid":"0000-0001-7388-9590","position":16,"is_corresponding":false},{"id":662296,"name":"Ghazaleh Sadri‐Vakili","orcid":"0000-0003-3435-3544","position":17,"is_corresponding":false},{"id":662286,"name":"Tiziana Petrozziello","orcid":"0000-0002-5487-1667","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:03:50.608887Z","pmid":"39500625","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":[]}