{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:02:52Z","timestamp":1787022172439,"version":"build-2736575974"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009469","name":"Conseil R\u00c3\u00a9gional du Centre-Val de Loire","doi-asserted-by":"publisher","award":["ANR-10-LABX-53"],"award-info":[{"award-number":["ANR-10-LABX-53"]}],"id":[{"id":"10.13039\/501100009469","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006510","name":"ARSLA","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006510","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100031220","name":"LabEx MAbImprove","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100031220","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    TDP-43 proteinopathies are neurological disorders marked by the abnormal accumulation of TDP-43 in the cytoplasm. This mislocalization disrupts the normal function of the protein. In most cases, it is the wildtype (wt) form of the protein that is involved. An untargeted high-throughput screen of a single-chain variable fragment (scFv) library was performed using phage display against human full-length wt TDP-43. Two scFvs (B1 and D7) were retained following cellular expression (then termed intrabodies) and colocalization with cytoplasmic TDP-43\n                    <jats:italic>\n                      <jats:italic>in vitro.<\/jats:italic>\n                    <\/jats:italic>\n                    We generated a 3D structure of full length wt TDP-43\n                    <jats:italic>\n                      <jats:italic>in silico<\/jats:italic>\n                    <\/jats:italic>\n                    , and used it for epitope mapping. In a cellular model of TDP-43 proteinopathy, D7 enhanced the proteasomal degradation of the insoluble 35-kDa C-terminal fragment of TDP-43 and reversed some TDP-43-induced metabolomic alterations, particularly relating to the lipid metabolism. Our findings offer a new scFv intrabody that bind to human wtTDP-43 and modify cellular pathways associated with TDP-43 proteinopathies.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0322021","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T17:22:46Z","timestamp":1754328166000},"page":"e0322021","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["scFv intrabody targeting wildtype TDP-43 presents protective effects in a cellular model of TDP-43 proteinopathy"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5270-155X","authenticated-orcid":true,"given":"Yara","family":"Al Ojaimi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Hergesheimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna 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Mehdipour","year":"2020","journal-title":"Immunology"},{"issue":"1","key":"pone.0322021.ref032","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-023-40630-7","article-title":"Subtractive panning for the isolation of monoclonal PEPITEM peptide antibody by phage display","volume":"13","author":"M Alassiri","year":"2023","journal-title":"Sci Rep"},{"issue":"5","key":"pone.0322021.ref033","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S1359-0278(98)00044-3","article-title":"Proteolytic selection for protein folding using filamentous bacteriophages","volume":"3","author":"P Kristensen","year":"1998","journal-title":"Fold Des"},{"issue":"28","key":"pone.0322021.ref034","doi-asserted-by":"crossref","first-page":"11992","DOI":"10.1074\/jbc.M117.775965","article-title":"Point mutations in the N-terminal domain of transactive response DNA-binding protein 43\u2009kDa (TDP-43) compromise its stability, dimerization, and functions","volume":"292","author":"M Mompe\u00e1n","year":"2017","journal-title":"J Biol Chem"},{"issue":"19","key":"pone.0322021.ref035","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1016\/j.jmb.2015.05.020","article-title":"The Signature of the Five-Stranded vRRM Fold Defined by Functional, Structural and Computational Analysis of the hnRNP L Protein","volume":"427","author":"M Blatter","year":"2015","journal-title":"J Mol Biol"},{"issue":"12","key":"pone.0322021.ref036","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/nsmb.2698","article-title":"Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43","volume":"20","author":"PJ Lukavsky","year":"2013","journal-title":"Nat Struct Mol Biol"},{"issue":"1","key":"pone.0322021.ref037","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/s41467-017-01241-9","article-title":"CryoEM structure of Saccharomyces cerevisiae U1 snRNP offers insight into alternative splicing","volume":"8","author":"X Li","year":"2017","journal-title":"Nat Commun"},{"issue":"7","key":"pone.0322021.ref038","doi-asserted-by":"crossref","first-page":"3826","DOI":"10.1093\/nar\/gkv156","article-title":"The structure of human SFPQ reveals a coiled-coil mediated polymer essential for functional aggregation in gene regulation","volume":"43","author":"M Lee","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"10","key":"pone.0322021.ref039","doi-asserted-by":"crossref","first-page":"3096","DOI":"10.4049\/jimmunol.1701722","article-title":"MAbTope: A Method for Improved Epitope Mapping","volume":"201","author":"T Bourquard","year":"2018","journal-title":"J Immunol"},{"key":"pone.0322021.ref040","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jpba.2017.03.068","article-title":"Workflow methodology for rat brain metabolome exploration using NMR, LC-MS and GC-MS analytical platforms","volume":"142","author":"B Di\u00e9m\u00e9","year":"2017","journal-title":"J Pharm Biomed 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Gautam","year":"2022","journal-title":"Sci Rep"},{"issue":"4","key":"pone.0322021.ref059","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/nan.12681","article-title":"Lipid alterations in human frontal cortex in ALS-FTLD-TDP43 proteinopathy spectrum are partly related to peroxisome impairment","volume":"47","author":"P Andr\u00e9s-Benito","year":"2021","journal-title":"Neuropathol Appl Neurobiol"},{"key":"pone.0322021.ref060","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2018.00182","article-title":"Medium-Chain Fatty Acids, Beta-Hydroxybutyric Acid and Genetic Modulation of the Carnitine Shuttle Are Protective in a Drosophila Model of ALS Based on TDP-43","volume":"11","author":"E Manzo","year":"2018","journal-title":"Front Mol Neurosci"},{"issue":"12","key":"pone.0322021.ref061","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1093\/brain\/awac025","article-title":"Metabolomics identifies shared lipid pathways in independent amyotrophic lateral sclerosis cohorts","volume":"145","author":"SA Goutman","year":"2022","journal-title":"Brain"},{"issue":"1","key":"pone.0322021.ref062","doi-asserted-by":"crossref","first-page":"17652","DOI":"10.1038\/s41598-017-17389-9","article-title":"Lipidomics Reveals Cerebrospinal-Fluid Signatures of ALS","volume":"7","author":"H Blasco","year":"2017","journal-title":"Sci Rep"},{"issue":"3","key":"pone.0322021.ref063","article-title":"Lipidomic traits of plasma and cerebrospinal fluid in amyotrophic lateral sclerosis correlate with disease progression","volume":"3","author":"J Sol","year":"2021","journal-title":"Brain Commun"},{"key":"pone.0322021.ref064","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s11010-010-0472-z","article-title":"L-carnitine is essential to beta-oxidation of quarried fatty acid from mitochondrial membrane by PLA(2)","volume":"342","author":"H Yano","year":"2010","journal-title":"Mol Cell Biochem"},{"issue":"8","key":"pone.0322021.ref065","first-page":"1725","article-title":"Cell senescence, loss of splicing, and lipid metabolism in TDP-43-related neurodegenerative processes","volume":"18","author":"P Torres","year":"2023","journal-title":"Neural Regen Res"},{"issue":"1","key":"pone.0322021.ref066","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/s42003-021-02034-z","article-title":"Downregulating carnitine palmitoyl transferase 1 affects disease progression in the SOD1 G93A mouse model of ALS","volume":"4","author":"MS Trabjerg","year":"2021","journal-title":"Commun Biol"}],"container-title":["PLOS 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