FIGURE 1: Therapeutic strategies to limit protein aggregation based disorders.

Many neurodegeneration disorders are characterized by increased protein aggregation of diseased associated proteins like α-synuclein and TDP-43. The yeast specific disaggregase Hsp104 and its variants (green) have been shown to be an effective in limiting inclusion formation and accumulation. Hsp104 acts on the inclusion to dissolve and restore them to the properly folded soluble form (TDP-43) as well as eliminate toxic soluble oligomeric forms (α-synuclein) of the protein. Additionally, caspase/metacaspase family of proteases (red) have also been shown to limit inclusion formation by directly cleaving the disease associated protein (TDP-43), which is subsequently degraded by the proteasome.