Loss of Sigma-1 Receptor Chaperone Promotes Astrocytosis and Enhances the Nrf2 Antioxidant Defense

Figure 6

The proposed model for imbalanced interplay between neurons and astrocytes in Sig-1R deficiency pathologies. In the normal state, astrocytes maintain the homeostasis and functions of the neuronal cells. In the state of Sig-1R deficiency, an increased astrocyte population is seen at the early stage to cope with the stressful conditions, but this later becomes harmful to the neuronal cells and leads to neuronal loss. The ubiquitinated proteins are accumulated during this process and disrupt the proteostasis. The enhanced Nrf2 here may represent another compensatory mechanism via an as yet unknown mechanism.