Figure 6. A model for the involvement of ER stress in TDP-43 proteinopathies.

ER stress activation causes accumulation of cytoplasmic TDP-43, and induction of TDP-43-positive SGs, which could lead to inclusion formation and neuron death in disease. ER stress may also lead to cell death via apoptotic signalling involving the transcription factor CHOP, independent of SGs and inclusion formation. Additionally, TDP-43 shows increased association with the chaperone PDI in disease. Pharmacological agents used in this study are shown italicised in blue.