{"doi":"10.1016/j.neuropharm.2019.01.023","title":"Multiple molecular pathways stimulating macroautophagy protect from alpha-synuclein-induced toxicity in human neurons","abstract":null,"journal":"Neuropharmacology","year":2019,"id":604805,"datarank":0.6253606935400514,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.17600085250695274,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.17600085250695274,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":11,"citers_with_citation_signal":9,"citers_with_endowment":9,"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":1551875,"name":"Natascha Fussi","orcid":null,"position":1,"is_corresponding":false},{"id":1551877,"name":"Thomas W. Rösler","orcid":null,"position":2,"is_corresponding":false},{"id":7259,"name":"Wolfgang Wurst","orcid":"0000-0003-4422-7410","position":3,"is_corresponding":false},{"id":247714,"name":"Christian Behrends","orcid":"0000-0002-9184-7607","position":4,"is_corresponding":false},{"id":84353,"name":"Günter U. Höglinger","orcid":"0000-0001-7587-6187","position":5,"is_corresponding":false},{"id":913224,"name":"Matthias Höllerhage","orcid":"0000-0002-5333-0121","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Multiple molecular pathways stimulating macroautophagy protect from alpha-synuclein-induced toxicity in human neurons","abstract":"Pathological aggregates of alpha-synuclein are the common hallmarks of synucleinopathies, including Parkinson's disease. There is currently no disease-modifying therapy approved for neurodegenerative synucleinopathies. The induction of macroautophagy by small compounds may be a strategy to reduce the cellular alpha-synuclein burden and to confer neuroprotection. Therefore, in the present study, we investigated a broad spectrum of druggable molecular signaling pathways reported to induce macroautophagy in human cells and compared their protective efficacy against alpha-synuclein-induced toxicity in cultured human postmitotic dopaminergic neurons. Several compounds affecting different pathways were able to activate macroautophagy. All compounds that activated autophagy also protected against alpha-synuclein-induced toxicity. The compounds with the lowest effective concentrations were PI-103, L-690,330, and NF 449, making them particularly interesting for further investigations, including in vivo models. Our findings demonstrate that activation of macroautophagy, as a neuroprotective approach in synucleinopathies, is accessible to pharmacotherapy. Moreover, pharmacological activation of macroautophagy via diverse signaling pathways is effective to protect human dopaminergic neurons against alpha-synuclein-induced toxicity.","is_dataset_classified":null,"base_score":2.995732273553991,"endowment":2.995732273553991,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30731136","pmcid":null,"openalex_id":"https://openalex.org/W2912544573","authors":[],"funders":[{"funder_name":"Deutsche Forschungsgemeinschaft (DFG","grant_id":"HO2402/6-2","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft (DFG","grant_id":"HO2402/18-1","title":null},{"funder_name":"German Federal Ministry of Education and Research","grant_id":"01KU1403A","title":null},{"funder_name":"German Federal Ministry of Education and Research","grant_id":"01EK1605A","title":null},{"funder_name":"Bavarian Ministry for Education, Culture, Science and Art","grant_id":"8810001412","title":null},{"funder_name":"German Federal Ministry of Education and Research","grant_id":"031A430E","title":null},{"funder_name":"NOMIS Foundation","grant_id":"","title":null},{"funder_name":"ParkinsonFonds Germany","grant_id":"","title":null}],"total_grants":8,"fwci":1.7622,"citation_percentile":0.83780373,"influential_citations":0,"citation_trend":[{"year":2019,"count":1},{"year":2020,"count":2},{"year":2021,"count":4},{"year":2022,"count":5},{"year":2024,"count":4},{"year":2025,"count":2}],"oa_status":"closed","license":"https://www.elsevier.com/legal/tdmrep-license","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0028390819300243?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0028390819300243?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.neuropharm.2019.01.023","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30731136","host_type":"repository"},{"url":"https://mediatum.ub.tum.de/1586899","host_type":"repository"},{"url":"https://pub.dzne.de/search?p=id:%22DZNE-2020-00019%22","host_type":"repository"},{"url":"https://push-zb.helmholtz-munich.de/frontdoor.php?source_opus=55443","host_type":"repository"}],"fields_of_study":["Parkinson's Disease Mechanisms and Treatments","Autophagy in Disease and Therapy"],"mesh_terms":["Neuroprotection","Autophagy","Benzenesulfonates","Cell Line","Cell Survival","Diphosphonates","Furans","Humans","Microtubule-Associated Proteins","Parkinson Disease","Pyridines","Pyrimidines","Signal Transduction","alpha-Synuclein","Caspase 3","Caspase 7","Dopaminergic Neurons"],"keywords":["Synucleinopathies","Alpha-synuclein","Neuroprotection","Autophagy","Dopaminergic","Pharmacology","Parkinson's disease","Biology","Neuroscience","Cell biology","Medicine","Dopamine","Biochemistry","Disease","Internal medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T00:57:17.306328Z","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":[]}