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Research, Johns Hopkins University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013013","name":"Target ALS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013013","name":"Target ALS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Inclusions containing TAR DNA binding protein 43 (TDP-43) are a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). One of the disease-specific features of TDP-43 inclusions is the aberrant phosphorylation of TDP-43 at serines 409\/410 (pS409\/410). Here, we developed rabbit monoclonal antibodies (mAbs) that specifically detect pS409\/410-TDP-43 in multiple model systems and FTD\/ALS patient samples. Specifically, we identified three mAbs (26H10, 2E9 and 23A1) from spleen B cell clones that exhibit high specificity and sensitivity to pS409\/410-TDP-43 peptides in an ELISA assay. Biochemical analyses revealed that pS409\/410 of recombinant TDP-43 and of exogenous 25 kDa TDP-43 C-terminal fragments in cultured HEK293T cells are detected by all three mAbs. Moreover, the mAbs detect pS409\/410-positive TDP-43 inclusions in the brains of FTD\/ALS patients and mouse models of TDP-43 proteinopathy by immunohistochemistry. Our findings indicate that these mAbs are a valuable resource for investigating TDP-43 pathology both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.pone.0298080","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T17:49:34Z","timestamp":1713462574000},"page":"e0298080","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43"],"prefix":"10.1371","volume":"19","author":[{"given":"Paula","family":"Castellanos Otero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany 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TDP-43 in gene expression, splicing regulation, and human disease","volume":"13","author":"E Buratti","year":"2008","journal-title":"Front Biosci"},{"key":"pone.0298080.ref006","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.pneurobio.2016.09.004","article-title":"TDP-43\/FUS in motor neuron disease: Complexity and challenges","volume":"145","author":"EN Guerrero","year":"2016","journal-title":"Progress in neurobiology"},{"key":"pone.0298080.ref007","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00401-008-0477-9","article-title":"Phosphorylation of S409\/410 of TDP-43 is a consistent feature in all sporadic and familial forms of TDP-43 proteinopathies","volume":"117","author":"M Neumann","year":"2009","journal-title":"Acta neuropathologica"},{"issue":"3","key":"pone.0298080.ref008","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1080\/14728222.2018.1439923","article-title":"TDP-43 post-translational modifications in health and 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