FIGURE 2.

Proposed mechanisms by which endoplasmic reticulum stress signaling in astrocytes impacts the overall central nervous system (CNS) environment. Here, we propose a model where astrocytes experience endoplasmic reticulum stress during disease states, activating the unfolded protein response (UPR). UPR‐related molecules are upregulated in astrocytes, concomitant with inflammatory genes. Further, UPR‐activated astrocytes have reduced capacity to support neuronal synapses and activated UPR in astrocytes is associated with increased synaptic loss and lower numbers of neurons during disease. Further, astrocytes have the capacity to “transmit” endoplasmic reticulum (ER) stress to other neuronal cell types including other astrocytes, microglia, and neurons. Figure was created in Biorender