Maintaining a Healthy Proteome during Oxidative Stress

Abstract

Some of the most challenging stress conditions that organisms encounter during their lifetime involve the transient accumulation of reactive oxygen and chlorine species. Extremely reactive to amino acid side chains, these oxidants cause widespread protein unfolding and aggregation. It is therefore not surprising that cells draw on a variety of different strategies to counteract the damage and maintain a healthy proteome. Orchestrated largely by direct changes in the thiol oxidation status of key proteins, the response strategies involve all layers of protein protection. Reprogramming of basic biological functions helps decrease nascent protein synthesis and restore redox homeostasis. Mobilization of oxidative stress-activated chaperones and production of stress-resistant non-proteinaceous chaperones prevent irreversible protein aggregation. Finally, redox-controlled increase in proteasome activity removes any irreversibly damaged proteins. Together, these systems pave the way to restore protein homeostasis and enable organisms to survive stress conditions that are inevitable when living an aerobic lifestyle.

Proteasome‐mediated proteostasis: Novel medicinal and pharmacological strategies for diseases

“…Raising the proteasomal capacity of clearing the aggregated proteins has long been seen as a possible approach to tackle the problem of increased load of aberrant proteins, as happens in most of the neurodegenerative diseases . Proteasome could also be targeted to annihilate several detrimental effects of reactive oxygen species (ROS) generation under many pathogenic conditions . A recent example of proteasome targeting comes from cilostazol, a known phosphodiesterase 3 inhibitor drug, which improves cognitive functions in tauopathy mouse model via enhancing the proteasomal activities and restoring in the proteostasis .…”

“…105 Proteasome could also be targeted to annihilate several detrimental effects of reactive oxygen species (ROS) generation under many pathogenic conditions. 106 A recent example of proteasome targeting comes from cilostazol, a known phosphodiesterase 3 inhibitor drug, which improves cognitive functions in tauopathy mouse model via enhancing the proteasomal activities and restoring in the proteostasis. 107 In fact, enhancing the protease activities by using several kinds of strategies and small molecules has paved way for the development of future therapeutics and has given tremendous hope to neuroscientists, who are working in the area of neurodegeneration.…”

Large‐Scale Analysis of Redox‐Sensitive Conditionally Disordered Protein Regions Reveals Their Widespread Nature and Key Roles in High‐Level Eukaryotic Processes

“…Redox regulation is essential for the survival of all organisms, as cells constantly encounter the transient accumulation of reactive oxygen species (ROS). ROS may be generated exogenously or endogenously due to metabolic activity or inflammation, while subsequent oxidative damage can cause widespread protein unfolding and aggregation . It may also contribute to the pathogenesis of many different diseases, as well as to degenerative processes associated with aging .…”

“…ROS may be generated exogenously or endogenously due to metabolic activity or inflammation, while subsequent oxidative damage can cause widespread protein unfolding and aggregation. [8,9] It may also contribute to the pathogenesis of many different diseases, as well as to degenerative processes associated with aging. [10,11] However, ROS can also serve as cellular signaling molecules and regulate various biological processes such as the immune response, cell proliferation, development, and more.…”

Proteome Oxidative Modifications and Impairment of Specific Metabolic Pathways During Cellular Senescence and Aging

“…In this case, as in a number of age related diseases, ROS reach levels overwhelming cellular defenses capacities creating an oxidative stress and triggering proteome damage. Enabling protein homeostasis to cope with oxidative stress, particularly at the level of protein quality control, could be one of the major ways to fight against the senescence‐associated oxidative damages …”