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Using inhibition of misfolded SOD1 deposition onto mitochondria as an assay, a chaperone activity abundant in nonneuronal tissues is now purified and identified to be the multifunctional macrophage migration inhibitory factor (MIF), whose activities include an ATP-independent protein folding chaperone. Purified MIF is shown to directly inhibit mutant SOD1 misfolding. Elevating MIF in neuronal cells suppresses accumulation of misfolded SOD1 and its association with mitochondria and the ER and extends survival of mutant SOD1-expressing motor neurons. Accumulated MIF protein is identified to be low in motor neurons, implicating correspondingly low chaperone activity as a component of vulnerability to mutant SOD1 misfolding and supporting therapies to enhance intracellular MIF chaperone activity.","is_dataset_classified":null,"base_score":4.762173934797756,"endowment":4.762173934797756,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25801706","pmcid":"PMC4393372","openalex_id":"https://openalex.org/W2044659434","authors":[],"funders":[{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS027036","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS644912","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"P30 NS047101","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS27036","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS064492","title":null}],"total_grants":5,"fwci":5.9223,"citation_percentile":0.97050712,"influential_citations":0,"citation_trend":[{"year":2015,"count":9},{"year":2016,"count":18},{"year":2017,"count":10},{"year":2018,"count":10},{"year":2019,"count":9},{"year":2020,"count":11},{"year":2021,"count":12},{"year":2022,"count":11},{"year":2023,"count":5},{"year":2024,"count":12},{"year":2025,"count":8},{"year":2026,"count":1}],"oa_status":"bronze","license":"https://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"http://www.cell.com/article/S089662731500149X/pdf","host_type":"journal"},{"url":"http://www.cell.com/article/S089662731500149X/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S089662731500149X?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S089662731500149X?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.neuron.2015.02.034","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25801706","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4393372","host_type":"repository"},{"url":"https://escholarship.org/uc/item/51q408rz","host_type":"repository"}],"fields_of_study":["Macrophage Migration Inhibitory Factor","Acid Phosphatase","Animals","Cell Differentiation","Cells, Cultured","Choline O-Acetyltransferase","Endoplasmic Reticulum","Green Fluorescent Proteins","Humans","Induced Pluripotent Stem Cells","Isoenzymes","Liver","Macrophage Migration-Inhibitory Factors","Mice","Mice, Transgenic","Mitochondria","Motor Neurons","Mutation","Nerve Tissue Proteins","Protein Folding","Protein Transport","Rats","Rats, Transgenic","Ribosomal Proteins","Spinal Cord","Superoxide Dismutase","Superoxide Dismutase-1","Tartrate-Resistant Acid Phosphatase"],"mesh_terms":["Tartrate-Resistant Acid Phosphatase","Superoxide Dismutase-1","Acid Phosphatase","Animals","Cell Differentiation","Cells, Cultured","Choline O-Acetyltransferase","Endoplasmic Reticulum","Humans","Isoenzymes","Liver","Macrophage Migration-Inhibitory Factors","Mice, Transgenic","Mitochondria","Motor Neurons","Mutation","Nerve Tissue Proteins","Ribosomal Proteins","Spinal Cord","Superoxide Dismutase","Protein Folding","Protein Transport","Green Fluorescent Proteins","Mice","Rats","Rats, Transgenic","Induced Pluripotent Stem Cells"],"keywords":["SOD1","Chaperone (clinical)","Endoplasmic reticulum","Macrophage migration inhibitory factor","Cell biology","Mitochondrion","Intracellular","Unfolded protein response","Protein folding","Cytoplasm","Mutant","Amyotrophic lateral sclerosis","Protein aggregation","Biology","Chemistry","Biochemistry","Immunology","Medicine"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.19746121.v1","title":"Additional file 1 of Copper oxide nanoparticles trigger macrophage cell death with misfolding of Cu/Zn superoxide dismutase 1 (SOD1)","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19746121","title":"Additional file 1 of Copper oxide nanoparticles trigger macrophage cell death with misfolding of Cu/Zn superoxide dismutase 1 (SOD1)","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T18:24:27.530294Z","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":[]}