{"doi":"10.1101/2023.08.29.555300","title":"The A53T mutation in α-synuclein enhances pro-inflammatory activation in human microglia","abstract":"Parkinson's disease (PD) is characterized by the aggregation of α-synuclein into Lewy bodies and Lewy neurites in the brain. Microglia-driven neuroinflammation may contribute to neuronal death in PD, however the exact role of microglia remains unclear and has been understudied. The A53T mutation in the gene coding for α-synuclein has been linked to early-onset PD, and exposure to A53T-mutant human α-synuclein increases the potential for inflammation of murine microglia. To date, its effect has not been studied in human microglia. Here, we used 2-dimensional cultures of human iPSC-derived microglia and transplantation of these cells into the mouse brain to assess the effects of the A53T mutation on human microglia. We found that A53T-mutant human microglia had an intrinsically increased propensity towards pro-inflammatory activation upon inflammatory stimulus. Additionally, A53T mutant microglia showed a strong decrease in catalase expression in non-inflammatory conditions, and increased oxidative stress. Our results indicate that A53T mutant human microglia display cell-autonomous phenotypes that may worsen neuronal damage in early-onset PD.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":397177,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":503103,"name":"Bingbing Yuan","orcid":"0000-0002-8460-5124","position":1,"is_corresponding":false},{"id":1172778,"name":"Wenyu Chen","orcid":"0000-0001-8768-0042","position":2,"is_corresponding":false},{"id":292898,"name":"Tatsuya Osaki","orcid":"0000-0001-7174-0629","position":3,"is_corresponding":false},{"id":977632,"name":"Dongdong Fu","orcid":"0000-0002-1499-7409","position":4,"is_corresponding":false},{"id":977966,"name":"Carrie M. Garrett-Engele","orcid":null,"position":5,"is_corresponding":false},{"id":248411,"name":"Devon S. Svoboda","orcid":null,"position":6,"is_corresponding":false},{"id":751673,"name":"Kristin Andrykovich","orcid":null,"position":7,"is_corresponding":false},{"id":350055,"name":"Mriganka Sur","orcid":"0000-0003-2442-5671","position":8,"is_corresponding":false},{"id":30028,"name":"Rudolf Jaenisch","orcid":"0000-0002-2540-7099","position":9,"is_corresponding":false},{"id":977630,"name":"Marine Krzisch","orcid":"0000-0002-9964-7992","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:19:35.497854Z","pmid":"37693409","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":[]}