{"doi":"10.1073/pnas.2113489119","title":"Different α-synuclein prion strains cause dementia with Lewy bodies and multiple system atrophy","abstract":"The α-synuclein protein can adopt several different conformations that cause neurodegeneration. Different α-synuclein conformers cause at least three distinct α-synucleinopathies: multiple system atrophy (MSA), dementia with Lewy bodies (DLB), and Parkinson's disease (PD). In earlier studies, we transmitted MSA to transgenic (Tg) mice and cultured HEK cells both expressing mutant α-synuclein (A53T) but not to cells expressing α-synuclein (E46K). Now, we report that DLB is caused by a strain of α-synuclein prions that is distinct from MSA. Using cultured HEK cells expressing mutant α-synuclein (E46K), we found that DLB prions could be transmitted to these HEK cells. Our results argue that a third strain of α-synuclein prions likely causes PD, but further studies are needed to identify cells and/or Tg mice that express a mutant α-synuclein protein that is permissive for PD prion replication. Our findings suggest that other α-synuclein mutants should give further insights into α-synuclein prion replication, strain formation, and disease pathogenesis, all of which are likely required to discover effective drugs for the treatment of PD as well as the other α-synucleinopathies.","journal":"Proceedings of the National Academy of Sciences","year":2022,"id":235105,"datarank":0.6681520944380261,"base_score":4.454347296253507,"endowment":4.454347296253507,"self_citation_contribution":0.6681520944380261,"citation_network_contribution":0.0,"self_endowment_contribution":0.6681520944380261,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":85,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":852603,"name":"Joanne Lee","orcid":"0000-0001-8521-8989","position":1,"is_corresponding":false},{"id":853667,"name":"Octovia Monteiro","orcid":null,"position":2,"is_corresponding":false},{"id":471322,"name":"Amanda L. Woerman","orcid":"0000-0003-4029-1968","position":3,"is_corresponding":false},{"id":445931,"name":"Ann Lazar","orcid":"0000-0002-6341-0360","position":4,"is_corresponding":false},{"id":401479,"name":"Carlo Condello","orcid":"0000-0002-8454-5360","position":5,"is_corresponding":false},{"id":5843,"name":"Nick A. Paras","orcid":"0000-0001-5742-4056","position":6,"is_corresponding":false},{"id":5842,"name":"Stanley B. Prusiner","orcid":"0000-0003-1955-5498","position":7,"is_corresponding":false},{"id":5838,"name":"Jacob I. Ayers","orcid":"0000-0003-4544-2366","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:21:48.116752Z","pmid":"35115402","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":[]}