Neuronal overexpression of hTDP-43 in Caenorhabditis elegans mimics the cellular pathology commonly observed in TDP-43 proteinopathies.

ABSTRACT

Inclusions consisting of transactive response DNA-binding protein 43 (TDP-43) are a characteristic feature of amyotrophic lateral sclerosis (ALS). Caenorhabditis elegans has been instrumental in studying the underlying mechanisms of TDP-43 pathology. Here, we extend the possibilities of previous studies by examining a C. elegans model expressing human wild-type TDP-43 ( hTDP-43 ) pan-neuronally. We show that disease-related (hyper)phosphorylation and cytosolic localisation of hTDP-43 are present in hTDP-43 worms and that these features can be enhanced by adjusting the environmental temperature.