Oxidoreductases as Targets for Pulmonary Fibrosis
Pulmonary fibrosis is a disease where the lungs develop scarring, causing difficulty in breathing and reduced lung function. Oxidoreductases show promise as targets for pulmonary fibrosis due to their pivotal role in modulating oxidative stress and fibrosis.
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Pulmonary fibrosis is a disease where the lungs develop scarring, causing difficulty in breathing and reduced lung function. Pulmonary fibrosis is a widespread global health issue, affecting between 0.33 and 4.51 people per 10,000, depending on the region.¹ Survival rates after diagnosis are alarmingly low, highlighting the immediate need for new and effective treatments to improve patient outcomes.
The Role of Oxidative Stress in Pulmonary Fibrosis
Oxidative stress, resulting from an imbalance between oxidants and antioxidants, plays a pivotal role in the onset and progression of pulmonary fibrosis.² The distinct anatomy and function of lungs heighten their vulnerability to oxidative stress.³
In pulmonary fibrosis, oxidative stress arises from increased reactive oxygen species (ROS) production and weakened antioxidant defences,⁴ leading to fibrotic tissue deposition in the lungs. Given these insights, oxidoreductase enzymes are being explored as potential therapeutic targets.
Oxidoreductase enzymes maintain cellular redox balance, regulate oxidative stress, and can influence fibrotic tissue formation. Targeting these enzymes could help regulate oxidative stress pathways and potentially slow down pulmonary fibrosis progression. Here, we have utilized Causaly to identify oxidoreductases as potential targets of pulmonary fibrosis.
Enzymes as Targets for Pulmonary Fibrosis
According to Causaly, over 3000 targets for pulmonary fibrosis have been identified, with around 800 belonging to the enzyme target class. Enzymes play crucial roles in biological processes, and their dysfunction can contribute to disease by disrupting homeostasis in the body. These enzymes can be refined further by target subclass (Figure 1). This revealed hydrolases, transferases, and oxidoreductases as the groups with the most targets associated with pulmonary fibrosis.
Oxidoreductase Targets of Pulmonary Fibrosis
Among the enzymes targets identified by Causaly, approximately 120 were oxidoreductases. Targets can be prioritized by primary data coming from specific article sections. In this use case, we have filtered targets by results and findings section, narrowing down to around 30 oxidoreductases.
Using Causaly, targets can be filtered by linguistic evidence strength, enabling exploration of less studied but potentially interesting targets. Notably, succinate dehydrogenase and aldose reductase were two of the highest-ranking targets identified by evidence strength.
- Succinate Dehydrogenase is an enzyme involved in energy production. This enzyme increases succinate levels, promoting fibrosis by boosting glycolysis and reducing fatty acid oxidation. A recent in vivo study showed that the therapeutic targeting of succinate dehydrogenase prevents fibrosis formation and improves lung function.⁵
- Aldose Reductase is a member of the aldo-keto reductase superfamily, responsible for converting glucose to sorbitol. This enzyme has been implicated in various respiratory diseases, including acute lung injury. Recent studies demonstrated that epalrestat effectively suppressed the progression of pulmonary fibrosis by inhibiting aldose reductase.⁶
Conclusion
Oxidoreductase enzymes hold great promise as therapeutic targets for pulmonary fibrosis, a devastating lung disease in need of effective treatments. Targeting enzymes involved in oxidative stress may help reduce the build-up of fibrotic tissue in the lungs and improve patient outcomes.
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