FIGURE 5.

Proposed model of cross-links between ER stress, autophagy, and DA neurodegeneration. PD-associated genetic and environmental factors trigger ER stress, and ER stress activates the UPR and induces autophagy to alleviate cellular stress. However, these PD-associated factors commonly block autophagic flux and impair lysosomal functions, and these changes synergistically cause severe damage and degeneration of DA neurons. Relieving ER stress/UPR, enhancing the ER folding capacity, promoting autophagic flux, and restoring lysosomal functions are neuroprotective for PD. The combined intervention of ER stress/UPR and autophagy would be a more attractive therapeutic approach for PD.