Related Experiment Video
Updated: Sep 6, 2025
Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models
Published on: October 22, 2012
Inhibiting NADPH Oxidases to Target Vascular and Other Pathologies: An Update on Recent Experimental and Clinical
Anthony L Sylvester1, David X Zhang2, Sophia Ran3
1Department of Biology, University of Illinois at Springfield, Springfield, IL 62703, USA.
Abstract:
Reactive oxygen species (ROS) can be beneficial or harmful in health and disease. While low levels of ROS serve as signaling molecules to regulate vascular tone and the growth and proliferation of endothelial cells, elevated levels of ROS contribute to numerous pathologies, such as endothelial dysfunctions, colon cancer, and fibrosis. ROS and their cellular sources have been extensively studied as potential targets for clinical intervention. Whereas various ROS sources are important for different pathologies, four NADPH oxidases (NOX1, NOX2, NOX4, and NOX5) play a prominent role in homeostasis and disease. NOX1-generated ROS have been implicated in hypertension, suggesting that inhibition of NOX1 may be a promising therapeutic approach. NOX2 and NOX4 oxidases are of specific interest due to their role in producing extra- and intracellular hydrogen peroxide (H2O2). NOX4-released hydrogen peroxide activates NOX2, which in turn stimulates the release of mitochondrial ROS resulting in ROS-induced ROS release (RIRR) signaling. Increased ROS production from NOX5 contributes to atherosclerosis. This review aims to summarize recent findings on NOX enzymes and clinical trials inhibiting NADPH oxidases to target pathologies including diabetes, idiopathic pulmonary fibrosis (IPF), and primary biliary cholangitis (PBC).
Insights
Reactive oxygen species (ROS) are vital signaling molecules but harmful at high levels. This review explores NADPH oxidases (NOX) as therapeutic targets for diseases like hypertension, fibrosis, and diabetes.
Area of Science:
- Biochemistry
- Molecular Biology
- Pathophysiology
Background:
- Reactive oxygen species (ROS) play dual roles in health and disease, acting as signaling molecules at low levels and causing damage at elevated concentrations.
- Dysregulated ROS production is linked to various pathologies, including endothelial dysfunction, cancer, and fibrosis, making ROS sources key targets for intervention.
Purpose of the Study:
- To review recent findings on NADPH oxidase (NOX) enzymes, crucial sources of ROS in cellular homeostasis and disease.
- To summarize clinical trials investigating the inhibition of NOX enzymes for treating pathologies such as diabetes, idiopathic pulmonary fibrosis (IPF), and primary biliary cholangitis (PBC).
Main Methods:
- Literature review of recent research on NOX enzyme functions and their roles in disease.
- Analysis of clinical trial data for therapies targeting NOX enzymes.
Main Results:
- Specific NOX enzymes (NOX1, NOX2, NOX4, NOX5) are implicated in distinct pathologies like hypertension, atherosclerosis, and ROS-induced ROS release (RIRR) signaling.
- NOX4-derived hydrogen peroxide can activate NOX2, leading to mitochondrial ROS release, highlighting complex ROS signaling pathways.
Conclusions:
- NOX enzymes represent promising therapeutic targets for a range of diseases.
- Inhibiting specific NOX isoforms offers potential clinical strategies for managing conditions including diabetes, IPF, and PBC.
Related Concept Videos
01:23Antihypertensive Drugs: Vasodilators
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...