{"doi":"10.1073/pnas.1704351114","title":"SUMOylation and ubiquitination reciprocally regulate α-synuclein degradation and pathological aggregation","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>Our work uncovers SUMOylation as a major regulator of α-synuclein fate and pathological aggregation. SUMOylation promotes α-synuclein accumulation by counteracting α-synuclein ubiquitination and inhibiting its degradation. SUMOylation also directly causes aggregation of α-synuclein in vitro and in cells, and the effects are much more prominent with the α-synuclein disease mutants. Most importantly, levels of SUMOylated α-synuclein and components of the SUMOylation machinery increase severalfold in Parkinson’s disease (PD) brains and are present in Lewy bodies. Our data indicate a major role of SUMOylation in the pathological aggregation of α-synuclein and Lewy body formation. Therefore, SUMOylation blockers provide a strategy to prevent intracellular α-synuclein accumulation, aggregation, and spreading in PD.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2017,"id":603540,"datarank":0.782240363641348,"base_score":5.214935757608986,"endowment":5.214935757608986,"self_citation_contribution":0.782240363641348,"citation_network_contribution":0.0,"self_endowment_contribution":0.782240363641348,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":183,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1548228,"name":"Raymonde Szargel","orcid":null,"position":1,"is_corresponding":false},{"id":1548229,"name":"Vered Shani","orcid":null,"position":2,"is_corresponding":false},{"id":1548230,"name":"Haya Hamza","orcid":null,"position":3,"is_corresponding":false},{"id":1548231,"name":"Mor Savyon","orcid":null,"position":4,"is_corresponding":false},{"id":1548232,"name":"Fatimah Abd Elghani","orcid":null,"position":5,"is_corresponding":false},{"id":361971,"name":"Rina Bandopadhyay","orcid":"0000-0003-3502-8815","position":6,"is_corresponding":false},{"id":1246157,"name":"Simone Engelender","orcid":"0000-0001-7401-6855","position":7,"is_corresponding":false},{"id":1548227,"name":"Ruth Rott","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"SUMOylation and ubiquitination reciprocally regulate α-synuclein degradation and pathological aggregation","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>Our work uncovers SUMOylation as a major regulator of α-synuclein fate and pathological aggregation. SUMOylation promotes α-synuclein accumulation by counteracting α-synuclein ubiquitination and inhibiting its degradation. SUMOylation also directly causes aggregation of α-synuclein in vitro and in cells, and the effects are much more prominent with the α-synuclein disease mutants. Most importantly, levels of SUMOylated α-synuclein and components of the SUMOylation machinery increase severalfold in Parkinson’s disease (PD) brains and are present in Lewy bodies. Our data indicate a major role of SUMOylation in the pathological aggregation of α-synuclein and Lewy body formation. Therefore, SUMOylation blockers provide a strategy to prevent intracellular α-synuclein accumulation, aggregation, and spreading in PD.</jats:p>","is_dataset_classified":null,"base_score":5.214935757608986,"endowment":5.214935757608986,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29180403","pmcid":"PMC5740625","openalex_id":"https://openalex.org/W2768197807","authors":[],"funders":[{"funder_name":"Israel Academy of Sciences and Humanities","grant_id":"1790/14","title":null},{"funder_name":"Wellcome","grant_id":"WT089698","title":null},{"funder_name":"Medical Research Council","grant_id":"MR/M02492X/1","title":null},{"funder_name":"Wellcome Trust","grant_id":"","title":null},{"funder_name":"Wellcome Trust","grant_id":"","title":null}],"total_grants":5,"fwci":6.2832,"citation_percentile":0.97536259,"influential_citations":0,"citation_trend":[{"year":2018,"count":7},{"year":2019,"count":24},{"year":2020,"count":31},{"year":2021,"count":28},{"year":2022,"count":22},{"year":2023,"count":15},{"year":2024,"count":24},{"year":2025,"count":19},{"year":2026,"count":12}],"oa_status":"closed","license":"http://www.pnas.org/site/aboutpnas/licenses.xhtml","oa_locations":[{"url":"http://www.pnas.org/syndication/doi/10.1073/pnas.1704351114","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1704351114","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1704351114","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29180403","host_type":"repository"},{"url":"https://discovery.ucl.ac.uk/id/eprint/10032511/","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5740625","host_type":"repository"}],"fields_of_study":["Ubiquitin and proteasome pathways","Autophagy in Disease and Therapy","Histone Deacetylase Inhibitors Research","Animals","Cells, Cultured","HEK293 Cells","Humans","Neurons","Parkinson Disease","Protein Inhibitors of Activated STAT","Proteolysis","Rats, Sprague-Dawley","Salicylates","Substantia Nigra","Sumoylation","alpha-Synuclein"],"mesh_terms":["Animals","Cells, Cultured","Humans","Neurons","Parkinson Disease","Salicylates","Substantia Nigra","Rats, Sprague-Dawley","Protein Inhibitors of Activated STAT","alpha-Synuclein","HEK293 Cells","Sumoylation","Proteolysis"],"keywords":["SUMO protein","Ubiquitin","NEDD4","Cell biology","Proteasome","Protein aggregation","Ubiquitin ligase","Chemistry","Alpha-synuclein","Synuclein","Biology","Parkinson's disease","Biochemistry","Disease","Medicine","Internal medicine","Ubiquitination","Aggregation","sumoylation","α-synuclein","Parkinson’s Disease"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T22:11:26.487940Z","pmid":null,"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":[]}