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Here, we investigated the crosstalk between large (LVs) and small (SVs) EVs and PQC in the disposal of TDP-43 and its FTLD and ALS-associated C-terminal fragments (TDP-35 and TDP-25). By taking advantage of neuronal cells (NSC-34 cells), we demonstrated that both EVs types, but particularly LVs, contained TDP-43, TDP-35 and TDP-25. When the PQC system was inhibited, as it occurs in NDs, we found that TDP-35 and TDP-25 secretion via EVs increased. In line with this observation, we specifically detected TDP-35 in EVs derived from plasma of FTLD patients. Moreover, we demonstrated that both neuronal and plasma-derived EVs transported components of the chaperone-assisted selective autophagy (CASA) complex (HSP70, BAG3 and HSPB8). Neuronal EVs also contained the autophagy-related MAP1LC3B-II protein. Notably, we found that, under PQC inhibition, HSPB8, BAG3 and MAP1LC3B-II secretion paralleled that of TDP-43 species. Taken together, our data highlight the role of EVs, particularly of LVs, in the disposal of disease-associated TDP-43 species, and suggest a possible new role for the CASA complex in NDs.<\/jats:p>","DOI":"10.3390\/cells11030516","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T05:42:33Z","timestamp":1643866953000},"page":"516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Neurodegenerative Disease-Associated TDP-43 Fragments Are Extracellularly Secreted with CASA Complex Proteins"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3842-8243","authenticated-orcid":false,"given":"Elena","family":"Casarotto","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Department of Excellence 2018\u20132022, Universit\u00e0 degli Studi di Milano, Via Balzaretti 9, 20133 Milano (MI), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5061-683X","authenticated-orcid":false,"given":"Daisy","family":"Sproviero","sequence":"additional","affiliation":[{"name":"Genomic and Post-Genomic Center, IRCCS\u2014Mondino Foundation, via Mondino 2, 27100 Pavia (PV), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Corridori","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Department of Excellence 2018\u20132022, Universit\u00e0 degli Studi di Milano, Via Balzaretti 9, 20133 Milano (MI), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Gagliani","sequence":"additional","affiliation":[{"name":"Cellular Electron Microscopy Laboratory, Department of Experimental Medicine (DIMES), University of Genoa, Via Antonio de Toni 14, 16132 Genova (GE), 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Neuropathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41582-020-0333-7","article-title":"Protein Transmission in Neurodegenerative Disease","volume":"16","author":"Peng","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1038\/s12276-020-00513-7","article-title":"The Role of TDP-43 Propagation in Neurodegenerative Diseases: Integrating Insights from Clinical and Experimental Studies","volume":"52","author":"Jo","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.conb.2020.02.009","article-title":"Potential Benefit of Manipulating Protein Quality Control Systems in Neurodegenerative Diseases","volume":"61","author":"Luh","year":"2020","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.2147\/CIA.S288415","article-title":"Recent Advances on Extracellular Vesicles in Central Nervous System Diseases","volume":"16","author":"Jin","year":"2021","journal-title":"Clin. Interv. Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e106389","DOI":"10.15252\/embj.2020106389","article-title":"Proteostatic Imbalance and Protein Spreading in Amyotrophic Lateral Sclerosis","volume":"40","author":"Cicardi","year":"2021","journal-title":"EMBO J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/jnc.15288","article-title":"Exosomes in Parkinson Disease","volume":"157","author":"Pinnell","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.molmed.2020.03.012","article-title":"Cell-to-Cell Transmission of Tau and \u03b1-Synuclein","volume":"26","author":"Uemura","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"jcs243139","DOI":"10.1242\/jcs.243139","article-title":"Extracellular Vesicles\u2014Propagators of Neuropathology and Sources of Potential Biomarkers and Therapeutics for Neurodegenerative Diseases","volume":"133","author":"Vassileff","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41556-018-0250-9","article-title":"Specificities of Secretion and Uptake of Exosomes and Other Extracellular Vesicles for Cell-to-Cell Communication","volume":"21","author":"Mathieu","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"262.e1","DOI":"10.1016\/j.cell.2020.04.054","article-title":"SnapShot: Extracellular Vesicles","volume":"182","author":"Cocozza","year":"2020","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal Information for Studies of Extracellular Vesicles 2018 (MISEV2018): A Position Statement of the International Society for Extracellular Vesicles and Update of the MISEV2014 Guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"595515","DOI":"10.3389\/fcell.2020.595515","article-title":"Hijacking Endocytosis and Autophagy in Extracellular Vesicle Communication: Where the Inside Meets the Outside","volume":"8","author":"Pedrioli","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Buratta, S., Tancini, B., Sagini, K., Delo, F., Chiaradia, E., Urbanelli, L., and Emiliani, C. (2020). Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072576"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1080\/15548627.2020.1760057","article-title":"The LC3-Conjugation Machinery Specifies Cargo Loading and Secretion of Extracellular Vesicles","volume":"16","author":"Klionsky","year":"2020","journal-title":"Autophagy"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1080\/15548627.2020.1756557","article-title":"LC3-Dependent Extracellular Vesicle Loading and Secretion (LDELS)","volume":"16","author":"Leidal","year":"2020","journal-title":"Autophagy"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41556-019-0450-y","article-title":"The LC3-Conjugation Machinery Specifies the Loading of RNA-Binding Proteins into Extracellular Vesicles","volume":"22","author":"Leidal","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1093\/brain\/aww237","article-title":"Exosome Secretion Is a Key Pathway for Clearance of Pathological TDP-43","volume":"139","author":"Iguchi","year":"2016","journal-title":"Brain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3389\/fnins.2018.00487","article-title":"Pathological Proteins Are Transported by Extracellular Vesicles of Sporadic Amyotrophic Lateral Sclerosis Patients","volume":"12","author":"Sproviero","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7789","DOI":"10.1007\/s12035-018-0947-6","article-title":"Towards a TDP-43-Based Biomarker for ALS and FTLD","volume":"55","author":"Feneberg","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"24178","DOI":"10.18632\/oncotarget.4680","article-title":"Exposure to ALS-FTD-CSF Generates TDP-43 Aggregates in Glioblastoma Cells through Exosomes and TNTs-like Structure","volume":"6","author":"Ding","year":"2015","journal-title":"Oncotarget"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1083\/jcb.201504057","article-title":"TDP-43 Is Intercellularly Transmitted across Axon Terminals","volume":"211","author":"Feiler","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sproviero, D., Gagliardi, S., Zucca, S., Arigoni, M., Giannini, M., Garofalo, M., Olivero, M., Dell\u2019orco, M., Pansarasa, O., and Bernuzzi, S. (2021). Different MiRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052737"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"344","DOI":"10.3389\/fnins.2019.00344","article-title":"Leukocyte Derived Microvesicles as Disease Progression Biomarkers in Slow Progressing Amyotrophic Lateral Sclerosis Patients","volume":"13","author":"Sproviero","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.bbrc.2006.10.093","article-title":"TDP-43 Is a Component of Ubiquitin-Positive Tau-Negative Inclusions in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis","volume":"351","author":"Arai","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.tins.2021.02.008","article-title":"Connecting TDP-43 Pathology with Neuropathy","volume":"44","author":"Klim","year":"2021","journal-title":"Trends Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3389\/fnmol.2019.00025","article-title":"Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis","volume":"12","author":"Prasad","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/jnc.13625","article-title":"Physiological Functions and Pathobiology of TDP-43 and FUS\/TLS Proteins","volume":"138","author":"Ratti","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"380","DOI":"10.2533\/chimia.2019.380","article-title":"Structural Transition, Function and Dysfunction of TDP-43 in Neurodegenerative Diseases","volume":"73","author":"Afroz","year":"2019","journal-title":"Chimia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3389\/fnmol.2019.00301","article-title":"Structural Insights Into TDP-43 and Effects of Post-Translational Modifications","volume":"12","author":"Scott","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3389\/fnins.2019.00335","article-title":"The Pathobiology of TDP-43 C-Terminal Fragments in ALS and FTLD","volume":"13","author":"Berning","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41593-018-0294-y","article-title":"TDP-43 Extracted from Frontotemporal Lobar Degeneration Subject Brains Displays Distinct Aggregate Assemblies and Neurotoxic Effects Reflecting Disease Progression Rates","volume":"22","author":"Maniecka","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wood, A., Gurfinkel, Y., Polain, N., Lamont, W., and Lyn Rea, S. (2021). Molecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094705"},{"key":"ref_35","first-page":"1263","article-title":"Differential Roles of the Ubiquitin Proteasome System and Autophagy in the Clearance of Soluble and Aggregated TDP-43 Species","volume":"127","author":"Scotter","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3908","DOI":"10.1093\/hmg\/ddw232","article-title":"The Chaperone HSPB8 Reduces the Accumulation of Truncated TDP-43 Species in Cells and Protects against TDP-43-Mediated Toxicity","volume":"25","author":"Crippa","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12390","DOI":"10.1038\/s41598-018-29658-2","article-title":"Tdp-25 Routing to Autophagy and Proteasome Ameliorates Its Aggregation in Amyotrophic Lateral Sclerosis Target Cells","volume":"8","author":"Cicardi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fnmol.2020.00019","article-title":"Chaperone Mediated Autophagy Degrades TDP-43 Protein and Is Affected by TDP-43 Aggregation","volume":"13","author":"Hormazabal","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_39","first-page":"3024","article-title":"Metabolism and Mis-Metabolism of the Neuropathological Signature Protein TDP-43","volume":"127","author":"Huang","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1016\/j.bbamcr.2016.05.005","article-title":"Transglutaminase Type 2-Dependent Selective Recruitment of Proteins into Exosomes under Stressful Cellular Conditions","volume":"1863","author":"Altuntas","year":"2016","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1080\/15548627.2018.1535292","article-title":"Trehalose Induces Autophagy via Lysosomal-Mediated TFEB Activation in Models of Motoneuron Degeneration","volume":"15","author":"Rusmini","year":"2019","journal-title":"Autophagy"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12192-017-0806-9","article-title":"The Small Heat Shock Protein B8 (HSPB8) Efficiently Removes Aggregating Species of Dipeptides Produced in C9ORF72-Related Neurodegenerative Diseases","volume":"23","author":"Cristofani","year":"2018","journal-title":"Cell Stress Chaperones"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1136\/jnnp-2013-306948","article-title":"New Criteria for Frontotemporal Dementia Syndromes: Clinical and Pathological Diagnostic Implications","volume":"85","author":"Chare","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1369\/00221554211026297","article-title":"Imaging of Endocytic Trafficking and Extracellular Vesicles Released Under Neratinib Treatment in ERBB2+ Breast Cancer Cells","volume":"69","author":"Santamaria","year":"2021","journal-title":"J. Histochem. Cytochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1080\/15548627.2017.1308985","article-title":"Inhibition of Retrograde Transport Modulates Misfolded Protein Accumulation and Clearance in Motoneuron Diseases","volume":"13","author":"Cristofani","year":"2017","journal-title":"Autophagy"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3620","DOI":"10.1073\/pnas.1312245111","article-title":"Intercellular Propagated Misfolding of Wild-Type Cu\/Zn Superoxide Dismutase Occurs via Exosome-Dependent and -Independent Mechanisms","volume":"111","author":"Grad","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","first-page":"273","article-title":"Exosomes from NSC-34 Cells Transfected with HSOD1-G93A Are Enriched in MiR-124 and Drive Alterations in Microglia Phenotype","volume":"1","author":"Sarko","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"922","DOI":"10.3892\/etm.2021.10354","article-title":"Prognostic Value of Plasma Exosomal Levels of Histone H3 Protein in Patients with Heat Stroke","volume":"22","author":"Li","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Cascella, R., Fani, G., Bigi, A., Chiti, F., and Cecchi, C. (2019). Partial Failure of Proteostasis Systems Counteracting TDP-43 Aggregates in Neurodegenerative Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153685"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"107498","DOI":"10.1016\/j.pharmthera.2020.107498","article-title":"A BAG\u2019s Life: Every Connection Matters in Cancer","volume":"209","author":"Mariotto","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.cub.2009.11.022","article-title":"Chaperone-Assisted Selective Autophagy Is Essential for Muscle Maintenance","volume":"20","author":"Arndt","year":"2010","journal-title":"Curr. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"958","DOI":"10.4161\/auto.6.7.13042","article-title":"A Role of Small Heat Shock Protein B8 (HspB8) in the Autophagic Removal of Misfolded Proteins Responsible for Neurodegenerative Diseases","volume":"7","author":"Crippa","year":"2010","journal-title":"Autophagy"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3389\/fnagi.2020.00191","article-title":"A Crucial Role for the Protein Quality Control System in Motor Neuron Diseases","volume":"12","author":"Cristofani","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1042\/BJ20061046","article-title":"Interaction of Mammalian Hsp22 with Lipid Membranes","volume":"401","author":"Chowdary","year":"2007","journal-title":"Biochem. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"22827","DOI":"10.1038\/srep22827","article-title":"Transcriptional Induction of the Heat Shock Protein B8 Mediates the Clearance of Misfolded Proteins Responsible for Motor Neuron Diseases","volume":"6","author":"Crippa","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1093\/hmg\/ddq257","article-title":"The Small Heat Shock Protein B8 (HspB8) Promotes Autophagic Removal of Misfolded Proteins Involved in Amyotrophic Lateral Sclerosis (ALS)","volume":"19","author":"Crippa","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.4161\/auto.29409","article-title":"BAG3 Induces the Sequestration of Proteasomal Clients into Cytoplasmic Puncta Implications for a Proteasome-to-Autophagy Switch","volume":"10","author":"Minoia","year":"2014","journal-title":"Autophagy"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"237","DOI":"10.4161\/auto.5407","article-title":"HspB8 and Bag3: A New Chaperone Complex Targeting Misfolded Proteins to Macroautophagy","volume":"4","author":"Carra","year":"2008","journal-title":"Autophagy"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.3233\/JAD-190545","article-title":"Exosomal HSP70 for Monitoring of Frontotemporal Dementia and Alzheimer\u2019s Disease: Clinical and FDG-PET Correlation","volume":"71","author":"Chanteloup","year":"2019","journal-title":"J. Alzheimer\u2019s Dis."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/3\/516\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:13:02Z","timestamp":1760134382000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/3\/516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,2]]},"references-count":59,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["cells11030516"],"URL":"https:\/\/doi.org\/10.3390\/cells11030516","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,2]]}}}