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Reactive astrocytes also release lipoproteins containing apolipoprotein E (APOE) and apolipoprotein J (APOJ) proteins and toxic lipids (saturated long-chain fatty acids and very long chain fatty acids), which trigger an endoplasmic reticulum stress response in neurons, with the concomitant activation of the eukaryotic translation initiation factor 2-alpha kinase (PERK), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6) signaling pathways and the activation of pro-apoptotic mediators (e.g., CCAAT/enhancer-binding protein homologous protein (CHOP), p53 up-regulated modulator of apoptosis (PUMA) and caspase 3), leading to neuronal cell death by apoptosis [17] (Figure 2)
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