Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43.

Autor: Castellanos Otero P; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America., Todd TW; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America., Shao W; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America., Jones CJ; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America., Huang K; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America., Daughrity LM; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America., Yue M; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America., Sheth U; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America.; Neurobiology of Disease Graduate Program, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America., Gendron TF; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America.; Neurobiology of Disease Graduate Program, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America., Prudencio M; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America.; Neurobiology of Disease Graduate Program, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America., Oskarsson B; Department of Neurology, Mayo Clinic, Jacksonville, Florida, United States of America., Dickson DW; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America.; Neurobiology of Disease Graduate Program, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America., Petrucelli L; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America.; Neurobiology of Disease Graduate Program, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America., Zhang YJ; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America.; Neurobiology of Disease Graduate Program, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Apr 18; Vol. 19 (4), pp. e0298080. Date of Electronic Publication: 2024 Apr 18 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0298080
Abstrakt: 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 in vitro and in vivo.
Competing Interests: The authors declare no competing interests.
(Copyright: © 2024 Castellanos Otero et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje