4-Hydroxynonenal induces persistent insolubilization of TDP-43 and alters its intracellular localization

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive degeneration of motor neurons. TDP-43 has been found to be a major component of ubiquitin-positive inclusions in ALS. Aberrant TDP-43, which is found in inclusions, is phosphorylated and is re-distributed from the nucleus to the cytoplasm. Alterations of TDP-43 protein, particularly insolubilization/aggregation and cytosolic distribution are thought...