TAR DNA-binding protein 43 aggregate (TDP-43 (aggregate form))

Aggregated TAR DNA-binding protein 43 (TDP-43) refers to the misfolded, insoluble, and often ubiquitinated and hyperphosphorylated forms of TDP-43 that accumulate as cytoplasmic protein inclusions in neurons and glia. TDP-43 is a highly conserved nuclear protein with two RNA recognition motifs and a glycine-rich C-terminal domain; it is essential for transcriptional repression, regulation of RNA splicing, and several aspects of RNA metabolism[3][1][5]. Aggregation and mislocalization of TDP-43 from the nucleus to the cytoplasm are pathological hallmarks of several neurodegenerative diseases, most prominently amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD)[3][6][4]. These aggregates disrupt normal cellular RNA homeostasis, lead to loss of TDP-43 nuclear function, and exert toxic gain-of-function effects that contribute to neuronal degeneration[3][4][6]. Disease-associated mutations in TDP-43, especially in its C-terminal prion-like domain, promote aggregation propensity[3][1][4]. Aggregated TDP-43 is a key pathological target under active investigation for disease-modifying therapies and biomarker strategies in neurodegeneration.

Other names

Aggregated TDP-43TDP-43 aggregateTDP-43 inclusionpathological TDP-43TDP-43 proteinopathy

Inhibitor of aggregation (molecules designed to block TDP-43 aggregation), Enhancer of clearance (agents increasing degradation or autophagy of TDP-43 aggregates)