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

Autor: Castellanos Otero, Paula, Todd, Tiffany W., Shao, Wei, Jones, Caroline J., Huang, Kexin, Daughrity, Lillian M., Yue, Mei, Sheth, Udit, Gendron, Tania F., Prudencio, Mercedes, Oskarsson, Björn, Dickson, Dennis W., Petrucelli, Leonard, Zhang, Yong-Jie
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Zdroj: PLoS ONE; 4/18/2024, Vol. 19 Issue 4, p1-14, 14p
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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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