New Insights on Heat Shock Proteins as Regulators of Reactive Oxygen Species Across Various Stressors in Diseases

Living beings are persistently challenged by stress. Stress can be induced by internal stressors and external stressors. External stressors, including radiation, heat, heavy metals, nutritional imbalances, infections, and psychological stress, can induce protein denaturation, leading to misfolded or aggregated proteins. These stressors often cause overproduction of reactive oxygen species (ROS), leading to oxidative stress following inflammation. This cascade causes and accelerates various disorders, such as diabetes, neurodegenerative, respiratory, cardiovascular, autoimmune. This disease, in turn, becomes internal stressors, perpetuating cellular dysfunction through sustained ROS production and chronic inflammation, creating a self-amplifying cycle that can lead to degenerative outcomes and organ failure. To cope with these stressors, cells initiate defense and protective mechanisms like antioxidant and heat shock proteins (HSPs). However, HSPs rapidly work to correct protein misfolding, mitigate oxidative damage, and reduce inflammation in response to external and internal stressors. HSPs increase the cell's efficiency to lower ROS levels and maintain the redox balance. On the other hand, cellular antioxidant regulatory role of HSPs includes suppressing apoptosis, modulating inflammatory signaling pathways (such as NF-κB, MAPK, JAK-SAT), inflammatory mediators (including TNF-α, IL-1β, IL-6) and maintaining proteostasis, Therefore, HSPs play a significant role in cellular survival and function under stress. However, targeting HSPs represents a promising future strategy for managing stress related conditions with a variety of diseases.