{"doi":"10.1002/jcb.25579","title":"Hyperosmotic Stress Induces Tau Proteolysis by Caspase‐3 Activation in SH‐SY5Y Cells","abstract":"<jats:title>ABSTRACT</jats:title><jats:sec><jats:label/><jats:p>Tau is a microtubule‐associated protein implicated in the pathogenesis of Alzheimer's disease and other related tauopathies. In this subset of neurodegenerative disorders, Tau auto‐assembles into insoluble fibrils that accumulate in neurons as paired helical filaments (PHFs), promoting cellular dysfunction and cytotoxic effects. Growing evidence suggests that abnormal post‐translational regulation, mainly hyperphosphorylation and aberrant cleavage, drives Tau to this pathological state. In this work we show that sorbitol‐induced hyperosmotic stress promotes Tau proteolysis in SH‐SY5Y neuroblastoma cells. The appearance of cleaved Tau was preceded by the activation of μ‐calpain, the proteasome system and caspase‐3. Tau proteolysis was completely prevented by caspase‐3 inhibition but unaffected by neither the proteasome system nor μ‐calpain activity blockade. Concomitantly, hyperosmotic stress induced apoptosis in SH‐SY5Y cells, which was efficiently avoided by the inhibition of caspase‐3 activity. Altogether, our results provide the first evidence that Tau protein is susceptible to caspase‐3 proteolysis under hyperosmotic stress and suggest a positive relationship between Tau proteolysis and apoptosis in SH‐SY5Y cells. J. Cell. Biochem. 117: 2781–2790, 2016. © 2016 Wiley Periodicals, Inc.</jats:p></jats:sec>","journal":"Journal of Cellular Biochemistry","year":2016,"id":677909,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"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":1771260,"name":"Montaña Caballero‐Bermejo","orcid":null,"position":1,"is_corresponding":false},{"id":1771264,"name":"Ricardo Argent","orcid":null,"position":2,"is_corresponding":false},{"id":1771268,"name":"Juan C. Alonso","orcid":null,"position":3,"is_corresponding":false},{"id":1771272,"name":"Ana Cuenda","orcid":null,"position":4,"is_corresponding":false},{"id":1771276,"name":"María J. Lorenzo","orcid":null,"position":5,"is_corresponding":false},{"id":1771279,"name":"Francisco Centeno","orcid":null,"position":6,"is_corresponding":false},{"id":1771255,"name":"Marta Olivera‐Santa Catalina","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Hyperosmotic Stress Induces Tau Proteolysis by Caspase‐3 Activation in SH‐SY5Y Cells","abstract":"<jats:title>ABSTRACT</jats:title><jats:sec><jats:label/><jats:p>Tau is a microtubule‐associated protein implicated in the pathogenesis of Alzheimer's disease and other related tauopathies. In this subset of neurodegenerative disorders, Tau auto‐assembles into insoluble fibrils that accumulate in neurons as paired helical filaments (PHFs), promoting cellular dysfunction and cytotoxic effects. Growing evidence suggests that abnormal post‐translational regulation, mainly hyperphosphorylation and aberrant cleavage, drives Tau to this pathological state. In this work we show that sorbitol‐induced hyperosmotic stress promotes Tau proteolysis in SH‐SY5Y neuroblastoma cells. The appearance of cleaved Tau was preceded by the activation of μ‐calpain, the proteasome system and caspase‐3. Tau proteolysis was completely prevented by caspase‐3 inhibition but unaffected by neither the proteasome system nor μ‐calpain activity blockade. Concomitantly, hyperosmotic stress induced apoptosis in SH‐SY5Y cells, which was efficiently avoided by the inhibition of caspase‐3 activity. Altogether, our results provide the first evidence that Tau protein is susceptible to caspase‐3 proteolysis under hyperosmotic stress and suggest a positive relationship between Tau proteolysis and apoptosis in SH‐SY5Y cells. J. Cell. Biochem. 117: 2781–2790, 2016. © 2016 Wiley Periodicals, Inc.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27152883","pmcid":null,"openalex_id":"https://openalex.org/W2380768677","authors":[],"funders":[{"funder_name":"Ministerio de Educación y Ciencia (Spain)","grant_id":"BFU2007-67577-C02-02/BMC","title":null},{"funder_name":"Junta de Extremadura (Spain)","grant_id":"GRU08018","title":null},{"funder_name":"Junta de Extremadura (Spain)","grant_id":"GRU09056","title":null},{"funder_name":"Junta de Extremadura (Spain)","grant_id":"GRU1018","title":null},{"funder_name":"Junta de Extremadura (Spain)","grant_id":"GR15164","title":null},{"funder_name":"FUNDESALUD","grant_id":"PRIS10018","title":null}],"total_grants":6,"fwci":0.9733,"citation_percentile":0.7653036,"influential_citations":0,"citation_trend":[{"year":2017,"count":1},{"year":2018,"count":2},{"year":2019,"count":2},{"year":2020,"count":3},{"year":2021,"count":1},{"year":2023,"count":1},{"year":2024,"count":2}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjcb.25579","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcb.25579","host_type":"publisher"},{"url":"https://doi.org/10.1002/jcb.25579","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27152883","host_type":"repository"}],"fields_of_study":["Alzheimer's disease research and treatments","Calpain Protease Function and Regulation","Endoplasmic Reticulum Stress and Disease"],"mesh_terms":["Enzyme Activation","Humans","Neuroblastoma","Osmotic Pressure","Phosphorylation","Tumor Cells, Cultured","Blotting, Western","Gene Expression Regulation, Neoplastic","tau Proteins","Apoptosis","Proteasome Endopeptidase Complex","Cell Proliferation","Caspase 3","Proteolysis"],"keywords":["Proteolysis","Calpain","SH-SY5Y","Proteasome","Cell biology","Apoptosis","Tau protein","Caspase","Hyperphosphorylation","Chemistry","Caspase 3","Biology","Biochemistry","Programmed cell death","Phosphorylation","Cell culture","Neuroblastoma","Internal medicine","Enzyme","Alzheimer's disease","Medicine","Caspase-3","Hyperosmotic Stress","Tau Proteolysis"],"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":"2026-08-17T04:42:09.422862Z","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":[]}