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

TL;DR

This paper explores how heat shock proteins help manage reactive oxygen species and reduce damage from various stressors, offering potential for treating stress-related diseases.

Contribution

The paper highlights the novel role of heat shock proteins in regulating reactive oxygen species across multiple stress-induced diseases.

Findings

Heat shock proteins reduce oxidative stress by stabilizing proteins and enhancing antioxidant activity.

HSPs modulate inflammatory pathways and mediators to protect cells from damage.

Targeting HSPs could be a promising strategy for managing stress-related disorders.

Abstract

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.

Reactive oxygen species, byproducts of cellular metabolism, are normally balanced by the cell's antioxidant defense system through redox homeostasis. Under stress (external and internal), excessive reactive oxygen species production disrupts redox homeostasis, leading to oxidative stress, inflammation, and cellular damage to DNA, lipids, and proteins. This damage triggers a vicious loop that increases reactive oxygen species levels. To counteract this, cells activate stress response pathways, including heat shock proteins, which play a vital role in protecting cellular components. Heat shock proteins stabilize damaged proteins, enhance antioxidant activity, and, when damage is irreversible, promote apoptosis to eliminate compromised cells, thereby protecting the integrity of cells and tissue under stress. Therefore, heat shock proteins are being explored as possible targets for reducing the negative effects in some disorders by increasing their levels.

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