Figure 1.

Protein misfolding in amyotrophic lateral sclerosis (ALS). (A) A normal cell depicting natively folded proteins in their proper location compared to ALS cells where proteins are found mislocalized and aggregated. (B) TAR DNA binding protein 43 (TDP-43) is mislocalized from the nucleus and aggregated within the cytosol (top left). Yeast models of ALS recapitulate these features of TDP-43 proteinopathy (top right). GFP-tagged TDP-43 wild-type expressed in yeast is found in cytoplasmic inclusions throughout the cell. Fused in sarcoma (FUS) proteinopathy is similar to that of TDP-43 (bottom left and right). (C) Superoxide dismutase (SOD1) is localized to the mitochondria and throughout the cytosol. In ALS, misfolded SOD1 is found aggregated at these locations.