Cellular pathways mediating ROS generation and ER stress

Cellular pathways mediating ROS generation and ER stress represent a complex signaling network rather than a single therapeutic target. Reactive Oxygen Species (ROS) are primarily generated by the mitochondrial electron transport chain and NADPH oxidase (NOX) enzymes, while Endoplasmic Reticulum (ER) stress is characterized by the accumulation of misfolded proteins, triggering the Unfolded Protein Response (UPR) via sensors like PERK, IRE1, and ATF6 (Hetz, 2012; Zeeshan et al., 2016). These two processes are highly interdependent; ROS can disrupt ER calcium homeostasis and protein folding, while ER stress can stimulate ROS production through the induction of ERO1 and mitochondrial dysfunction (Malhotra & Kaufman, 2007). Chronic activation of this ROS-ER stress axis is implicated in the pathogenesis of various conditions, including neurodegenerative diseases, type 2 diabetes, and cardiovascular disorders, often leading to programmed cell death (Bhat et al., 2015). Pharmacological intervention typically targets specific nodes within these pathways, such as using chemical chaperones like TUDCA to stabilize protein folding or antioxidants like N-acetylcysteine to neutralize ROS (Vang et al., 2014). Understanding the crosstalk between these pathways is crucial for developing therapies that can restore cellular proteostasis and redox balance.

Other names

ROS-ER stress axisOxidative stress and Unfolded Protein Response (UPR) crosstalkER-mitochondria signalingProteotoxic stress response

Modulation of oxidative stress levels through antioxidant activity and restoration of endoplasmic reticulum proteostasis via chemical chaperoning or inhibition of UPR sensors.