{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:09:52Z","timestamp":1793045392851,"version":"4.5.0"},"reference-count":71,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013928","name":"Millennium Institute on Immunology and Immunotherapy","doi-asserted-by":"crossref","award":["PROGRAMA ICM\u2014ANID, ICN2021_045"],"award-info":[{"award-number":["PROGRAMA ICM\u2014ANID, ICN2021_045"]}],"id":[{"id":"10.13039\/501100013928","id-type":"DOI","asserted-by":"crossref"}]},{"award":["PROGRAMA ICM\u2014ANID, ICN2021_045"],"award-info":[{"award-number":["PROGRAMA ICM\u2014ANID, ICN2021_045"]}],"id":[{"id":"https:\/\/ror.org\/05j6ybs54","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019783","name":"National Agency for Research and Development","doi-asserted-by":"crossref","award":["#1220110"],"award-info":[{"award-number":["#1220110"]}],"id":[{"id":"10.13039\/100019783","id-type":"DOI","asserted-by":"crossref"}]},{"award":["#1220110"],"award-info":[{"award-number":["#1220110"]}],"id":[{"id":"https:\/\/ror.org\/02ap3w078","id-type":"ROR","asserted-by":"publisher"}]},{"name":"ANID National Doctoral Fellowship","award":["#21212080"],"award-info":[{"award-number":["#21212080"]}]},{"name":"ICBM"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Protein\u2013protein interactions (PPIs) play a central role in regulating cellular processes. However, the identification and characterization of senescence-associated PPIs remain challenging. In this study, we developed and evaluated an integrative methodology based on selective proteomics to identify PPIs associated with cellular senescence induced by TMPRSS11a. We started from isolated proteins that co-immunoprecipitated with TMPRSS11a and were subsequently identified by mass spectrometry. Building on this dataset, we implemented a workflow combining selective proteomics, structural bioinformatics, and experimental validation. Using this approach, we investigated the interaction between the transmembrane serine protease TMPRSS11a and the chaperone HSPA8. Structural bioinformatics analyses were performed to identify potential residues involved in the interaction interface, and the proximity of the TMPRSS11a\u2013HSPA8 complex was evaluated using an in vitro proximity ligation assay. Our results provide evidence for an interaction between TMPRSS11a and HSPA8 and suggest its association with an enhanced senescence response. Overall, this study presents a workflow to investigate senescence-associated PPIs from proteomics-derived candidate proteins.<\/jats:p>","DOI":"10.3390\/biom16050714","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T16:46:18Z","timestamp":1779381978000},"page":"714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting Protein\u2013Protein Interactions (PPIs) to Drive Functional Annotation: An Integrative Methodology to Study Senescence-Associated PPIs Using TMPRSS11a as Model Interactor"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3735-7818","authenticated-orcid":false,"given":"Roberto","family":"Rosales-Rojas","sequence":"first","affiliation":[{"name":"Millennium Institute on Immunology and Immunotherapy, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago 8380453, Chile"},{"name":"Center for Bioinformatics, Simulation and Modeling, Faculty of Engineering, Universidad de Talca, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8157-5997","authenticated-orcid":false,"given":"Christian","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Millennium Institute on Immunology and Immunotherapy, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago 8380453, Chile"},{"name":"Instituo de Ciencias Biomedicas (ICBM), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8113-6758","authenticated-orcid":false,"given":"Mariela","family":"Gonz\u00e1lez-Avenda\u00f1o","sequence":"additional","affiliation":[{"name":"Center for Bioinformatics, Simulation and Modeling, Faculty of Engineering, Universidad de Talca, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1236-013X","authenticated-orcid":false,"given":"Ariela","family":"Vergara-Jaque","sequence":"additional","affiliation":[{"name":"Center for Bioinformatics, Simulation and Modeling, Faculty of Engineering, Universidad de Talca, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0456-0721","authenticated-orcid":false,"given":"M\u00f3nica","family":"C\u00e1ceres","sequence":"additional","affiliation":[{"name":"Millennium Institute on Immunology and Immunotherapy, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago 8380453, Chile"},{"name":"Instituo de Ciencias Biomedicas (ICBM), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cbpa.2020.07.003","article-title":"Protein engineering for selective proteomics","volume":"60","author":"Radziwon","year":"2021","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.1038\/s41467-024-50493-9","article-title":"Cell-selective proteomics reveal novel effectors secreted by an obligate intracellular bacterial pathogen","volume":"15","author":"Sanderlin","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1038\/s41467-023-38171-8","article-title":"Cell-selective proteomics segregates pancreatic cancer subtypes by extracellular proteins in tumors and circulation","volume":"14","author":"Swietlik","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.cbpa.2016.12.026","article-title":"Cell-selective proteomics for biological discovery","volume":"36","author":"Stone","year":"2017","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"848","DOI":"10.15252\/msb.20156351","article-title":"Fundamentals of protein interaction network mapping","volume":"11","author":"Snider","year":"2015","journal-title":"Mol. Syst. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3784","DOI":"10.1021\/acs.jcim.2c00457","article-title":"Hotspot Identification and Drug Design of Protein\u2013Protein Interaction Modulators Using the Fragment Molecular Orbital Method","volume":"62","author":"Monteleone","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/s41392-020-00315-3","article-title":"Recent advances in the development of protein\u2013protein interactions modulators: Mechanisms and clinical trials","volume":"5","author":"Lu","year":"2020","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1021\/pr201211w","article-title":"Analyzing Protein\u2013Protein Interaction Networks","volume":"11","author":"Koh","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41594-023-01148-8","article-title":"Structural biases in disordered proteins are prevalent in the cell","volume":"31","author":"Moses","year":"2024","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6580","DOI":"10.2741\/3175","article-title":"Understanding eukaryotic linear motifs and their role in cell signaling and regulation","volume":"13","author":"Diella","year":"2008","journal-title":"Front. Biosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.copbio.2006.08.002","article-title":"Peptides mediating interaction networks: New leads at last","volume":"17","author":"Neduva","year":"2006","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: An expanding universe","volume":"186","author":"Blasco","year":"2023","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1083\/jcb.201009094","article-title":"Four faces of cellular senescence","volume":"192","author":"Rodier","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s41580-020-00314-w","article-title":"Cellular senescence in ageing: From mechanisms to therapeutic opportunities","volume":"22","author":"Krizhanovsky","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Basisty, N., Kale, A., Jeon, O.H., Kuehnemann, C., Payne, T., Rao, C., Holtz, A., Shah, S., Sharma, V., and Ferrucci, L. (2020). A proteomic atlas of senescence-associated secretomes for aging biomarker development. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000599"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.cell.2019.10.005","article-title":"Cellular Senescence: Defining a Path Forward","volume":"179","author":"Gorgoulis","year":"2019","journal-title":"Cell"},{"key":"ref_18","first-page":"482","article-title":"Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence","volume":"11","author":"Weber","year":"2016","journal-title":"Redox Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.tcb.2020.07.002","article-title":"A Senescence-Centric View of Aging: Implications for Longevity and Disease","volume":"30","author":"Borghesan","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.cell.2017.05.015","article-title":"Senescence in Health and Disease","volume":"169","author":"He","year":"2017","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s10522-023-10084-5","article-title":"Application potential of senolytics in clinical treatment","volume":"25","author":"Li","year":"2023","journal-title":"Biogerontology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e21597","DOI":"10.1096\/fj.202002253RRR","article-title":"TMPRSS11a is a novel age-altered, tissue specific regulator of migration and wound healing","volume":"35","author":"Fernandez","year":"2021","journal-title":"FASEB J."},{"key":"ref_23","first-page":"213","article-title":"ECRG1 and Its Relationship with Esophageal Cancer: A Brief Review","volume":"36","author":"Rasool","year":"2013","journal-title":"Onkologie"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1177\/153537020623100110","article-title":"ECRG1, a Novel Candidate of Tumor Suppressor Gene in the Esophageal Carcinoma, Triggers a Senescent Program in NIH3T3 Cells","volume":"231","author":"Zhao","year":"2006","journal-title":"Exp. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/jcb.20025","article-title":"Induction of G1 cell cycle arrest and P15INK4b expression by ECRG1 through interaction with Miz-1","volume":"92","author":"Zhao","year":"2004","journal-title":"J. Cell. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.4161\/auto.26448","article-title":"HSPA8\/HSC70 chaperone protein","volume":"9","author":"Stricher","year":"2013","journal-title":"Autophagy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cell.2006.04.014","article-title":"Molecular chaperones and protein quality control","volume":"125","author":"Bukau","year":"2006","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1007\/s00018-004-4464-6","article-title":"Hsp70 chaperones: Cellular functions and molecular mechanism","volume":"62","author":"Mayer","year":"2005","journal-title":"Cell Mol. Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein\u2013protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s41596-019-0128-8","article-title":"Protocol Update for large-scale genome and gene function analysis with the PANTHER classification system (v.14.0)","volume":"14","author":"Mi","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/s41586-025-08592-0","article-title":"A compendium of human gene functions derived from evolutionary modelling","volume":"640","author":"Feuermann","year":"2025","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: Tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Gene Ontol. Consortium. Nat. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/nar\/28.1.33","article-title":"The COG database: A tool for genome-scale analysis of protein functions and evolution","volume":"28","author":"Tatusov","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1474-9726.2008.00442.x","article-title":"The Human Ageing Genomic Resources: Online databases and tools for biogerontologists","volume":"8","author":"Budovsky","year":"2009","journal-title":"Aging Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"D1353","DOI":"10.1093\/nar\/gkac1046","article-title":"The next-generation Open Targets Platform: Reimagined, redesigned, rebuilt","volume":"51","author":"Ochoa","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Avenda\u00f1o, M., Z\u00fa\u00f1iga-Almonacid, S., Silva, I., Lavanderos, B., Robinson, F., Rosales-Rojas, R., Dur\u00e1n-Verdugo, F., Gonz\u00e1lez, W., C\u00e1ceres, M., and Cerda, O. (2021). PPI-MASS: An Interactive Web Server to Identify Protein-Protein Interactions From Mass Spectrometry-Based Proteomics Data. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.701477"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41514-025-00200-9","article-title":"Characterization of senescence and nuclear reorganization in aging gingival cells","volume":"11","author":"Ormeno","year":"2025","journal-title":"npj Aging"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: Making protein folding accessible to all","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1038\/nbt.3988","article-title":"MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets","volume":"35","author":"Steinegger","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1111\/tra.12432","article-title":"Using HHsearch to tackle proteins of unknown function: A pilot study with PH domains","volume":"17","author":"Fidler","year":"2016","journal-title":"Traffic"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/prot.23175","article-title":"RaptorX: Exploiting structure information for protein alignment by statistical inference","volume":"79","author":"Peng","year":"2011","journal-title":"Proteins"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"167556","DOI":"10.1016\/j.jmb.2022.167556","article-title":"BIPSPI+: Mining Type-Specific Datasets of Protein Complexes to Improve Protein Binding Site Prediction","volume":"434","author":"Macias","year":"2022","journal-title":"J. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1146\/annurev.biochem.77.062906.171838","article-title":"Macromolecular modeling with rosetta","volume":"77","author":"Das","year":"2008","journal-title":"Annu. Rev. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chaudhury, S., Berrondo, M., Weitzner, B.D., Muthu, P., Bergman, H., and Gray, J.J. (2011). Benchmarking and Analysis of Protein Docking Performance in Rosetta v3.2. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022477"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3345","DOI":"10.1080\/00268976.2013.813594","article-title":"Using collective variables to drive molecular dynamics simulations","volume":"111","author":"Fiorin","year":"2013","journal-title":"Mol. Phys."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/jcc.20289","article-title":"Scalable Molecular Dynamics with NAMD","volume":"26","author":"Phillips","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/jcc.21367","article-title":"CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields","volume":"31","author":"Vanommeslaeghe","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4613","DOI":"10.1063\/1.470648","article-title":"Constant pressure molecular dynamics simulation: The Langevin piston method","volume":"103","author":"Feller","year":"1995","journal-title":"J. Chem. Phys."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N\u22c5log(N) method for Ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1021\/ct5010406","article-title":"Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning","volume":"11","author":"Hopkins","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4654","DOI":"10.1038\/s41467-023-40365-z","article-title":"Functional annotation of proteins for signaling network inference in non-model species","volume":"14","author":"Bhosale","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e2513219122","DOI":"10.1073\/pnas.2513219122","article-title":"Protein functional site annotation using local structure embeddings","volume":"122","author":"Derry","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1093\/bib\/bbz081","article-title":"Protein functional annotation of simultaneously improved stability, accuracy and false discovery rate achieved by a sequence-based deep learning","volume":"21","author":"Hong","year":"2019","journal-title":"Brief. Bioinform."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"The UniProt Consortium (2023). UniProt: The Universal Protein Knowledgebase in 2023. Nucleic Acids Res., 51, D523\u2013D531.","DOI":"10.1093\/nar\/gkac1052"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/978-1-0716-1613-0_8","article-title":"Tandem Affinity Purification (TAP) of Low-Abundance Protein Complexes in Filamentous Fungi Demonstrated Using Magnaporthe oryzae","volume":"2356","author":"Li","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_59","first-page":"55498","article-title":"Resolving Affinity Purified Protein Complexes by Blue Native PAGE and Protein Correlation Profiling","volume":"122","author":"Pardo","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"D730","DOI":"10.1093\/nar\/gkae1113","article-title":"The STRING database in 2025: Protein networks with directionality of regulation","volume":"53","author":"Szklarczyk","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1007\/s11357-021-00394-2","article-title":"Role of heat shock proteins in aging and chronic inflammatory diseases","volume":"43","author":"Gomez","year":"2021","journal-title":"GeroScience"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Loeffler, D.A., Klaver, A.C., Coffey, M.P., Aasly, J.O., and LeWitt, P.A. (2016). Age-Related Decrease in Heat Shock 70-kDa Protein 8 in Cerebrospinal Fluid Is Associated with Increased Oxidative Stress. Front. Aging Neurosci., 8.","DOI":"10.3389\/fnagi.2016.00178"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/s41422-023-00859-3","article-title":"HSPA8 acts as an amyloidase to suppress necroptosis by inhibiting and reversing functional amyloid formation","volume":"33","author":"Wu","year":"2023","journal-title":"Cell Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.tibs.2020.02.005","article-title":"Unfolded Protein Response (UPR) Controls Major Senescence Hallmarks","volume":"45","author":"Abbadie","year":"2020","journal-title":"Trends Biochem. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41581-022-00601-z","article-title":"Cellular senescence: The good, the bad and the unknown","volume":"18","author":"Huang","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"C415","DOI":"10.1152\/ajpcell.00334.2014","article-title":"The unfolded protein response and cellular senescence. A Review in the Theme: Cellular Mechanisms of Endoplasmic Reticulum Stress Signaling in Health and Disease","volume":"308","author":"Pluquet","year":"2015","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.mad.2017.08.003","article-title":"The ATF6\u03b1 arm of the Unfolded Protein Response mediates replicative senescence in human fibroblasts through a COX2\/prostaglandin E2 intracrine pathway","volume":"170","author":"Cormenier","year":"2018","journal-title":"Mech. Ageing Dev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1146\/annurev.biochem.052308.114844","article-title":"Biological and chemical approaches to diseases of proteostasis deficiency","volume":"78","author":"Powers","year":"2009","journal-title":"Annu. Rev. Biochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1038\/nm.4001","article-title":"Proteostasis and aging","volume":"21","author":"Kaushik","year":"2015","journal-title":"Nat. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1146\/annurev-biochem-060614-033955","article-title":"The biology of proteostasis in aging and disease","volume":"84","author":"Labbadia","year":"2015","journal-title":"Annu. Rev. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.tcb.2014.05.003","article-title":"Proteostasis impairment in protein-misfolding and -aggregation diseases","volume":"24","author":"Hipp","year":"2014","journal-title":"Trends Cell Biol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/714\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T04:25:16Z","timestamp":1779423916000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":71,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["biom16050714"],"URL":"https:\/\/doi.org\/10.3390\/biom16050714","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]}}}