Phospho-TDP43 (Ser409/410) Recombinant Rabbit mAb (S-3862)

Phospho-TDP43 (Ser409/410) refers to the abnormally phosphorylated form of the TAR DNA-binding protein 43 (TDP-43) at serine residues 409 and 410, which is widely recognized as the pathological hallmark and biochemical signature of TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Under physiological conditions, TDP-43 is predominantly nuclear and exists in a non-phosphorylated state; however, in disease, it becomes hyperphosphorylated at these C-terminal serine residues, leading to its mislocalization to the cytoplasm and incorporation into ubiquitin-positive inclusions. Studies using monoclonal antibodies specifically generated against the dual-phosphorylated Ser409/410 epitope (mAb pS409/410) have demonstrated that this modification is a highly consistent and specific feature of pathological TDP-43 across the entire spectrum of sporadic and familial TDP-43 proteinopathies, while normal nuclear TDP-43 remains unstained. Notably, phosphorylation at both Ser409 and Ser410 is required for antibody recognition, and casein kinase 1 (CK1) has been identified as a candidate kinase responsible for generating this pathological epitope. Functionally, this phosphorylation event promotes TDP-43 oligomerization and enhances its fibrillation propensity in vitro, contributing to the formation of the characteristic sarkosyl-insoluble, urea-soluble aggregates found in affected neurons and glial cells. Additionally, the phosphorylation status at these sites serves as a critical biomarker for the neuropathological diagnosis of TDP-43 proteinopathies and is increasingly recognized as a potential therapeutic target, with recent studies identifying CDC7 as another kinase capable of phosphorylating these residues and driving neurotoxicity in disease models.