Fig. 2
From: The role of TDP-43 mislocalization in amyotrophic lateral sclerosis
TDP-43 (Red) mislocalizes (partially or completely) from the nucleus to the cytoplasm due to genetic and/or environmental factors causing deleterious effects to the cell. Prolonged mislocalization promotes aggregation. Under physiological conditions the cell can clear small TDP-43 aggregates through proteasomal, endosomal, or autophagic degradation. Prolonged The accumulation of TDP-43 aggregates disrupts physiological functioning (e.g. sequestration of SQSTM1) thereby exacerbating pathology and promoting neuronal degeneration. Early interventions normalizing TDP-43 localization hold the potential to prevent cellular demise