The Interplay Between Ca2+ Homeostasis, Endoplasmic Reticulum Stress, and the Unfolded Protein Response in Human Diseases - PubMed
5 hours ago
- #calcium dyshomeostasis
- #ER stress
- #unfolded protein response
- ER Ca2+ homeostasis is crucial for protein folding and triggers the Unfolded Protein Response (UPR) when disrupted.
- Chronic dysregulation of the Ca2+-ER Stress-UPR network is linked to diseases like neurodegeneration, heart failure, and cancer.
- Key stress sensors (PERK, IRE1alpha, ATF6) engage in feedback loops that can restore balance or lead to apoptosis.
- The PERK-CHOP-SERCA2b circuit is a major driver of persistent Ca2+ depletion, with Mitochondria-Associated Membranes (MAMs) playing a role in lethal Ca2+ transfer.
- CHOP has context-dependent adaptive functions beyond its known role in apoptosis.
- The transition from adaptive to maladaptive UPR is a critical checkpoint in disease pathology.
- Potential therapeutic interventions include SERCA activators and selective UPR modulators to address Ca2+ signaling defects in ER stress-related disorders.