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In addition to the PERK-ATF4-CHOP axis, other key ER stress pathways, such as IRE1/XBP1 and ATF6 also contribute to the UPR, collectively managing protein misfolding and restoring homeostasis, or, if stress persists, trigger cell death ( Various studies targeting ER stress signaling pathways and components of the UPR have demonstrated that CHAC1 expression is upregulated downstream of the ATF4-dependent signaling pathway (Figure 4)

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Collectively, these findings suggest that adult WT mice exhibit greater resilience to stress compared to their adolescent counterparts, whereas aberrant anxiety susceptibility in KI mice emerges selectively during adulthoodpotentially due to the aberrant increase in CCK expression in the mPFC that occurs only in adulthood