Figure 4.

Model for roles of unfolded protein stress in neurodegeneration. Under unmitigated stress, as may be the case in many neurodegenerative diseases, the ER-UPR can induce cell death. The disruption or malfunction of the ER-UPR may also contribute to the development of important pathologies like neurodegenerative diseases. Although the data is unclear, the ER-UPR may induce mitochondrial stress (dashed line) through calcium signaling or other means. Mitochondrial stress is well known to induce apoptosis and contribute to neurodegeneration. We propose a model in which the MT-UPR stimulated by protein misfolding that is characteristic of neurodegenerative diseases may also play a role in cell death (dashed line).