Developing a novel strategy for COPD therapy by targeting Nrf2 and metabolism reprogramming simultaneously.

Area of Science:

• Pulmonary Medicine
• Molecular Biology
• Pharmacology

Background:

• Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability globally.
• Inflammation and oxidative stress are key factors in COPD pathogenesis.
• Metabolic dysfunction also contributes to COPD exacerbation, with limited therapeutic strategies.

Purpose of the Study:

• To introduce a novel therapeutic strategy for COPD targeting metabolic reprogramming.
• To evaluate the efficacy of CPUY192018, a nuclear factor erythroid-2-related factor 2 (Nrf2) activator, in COPD treatment.

Main Methods:

• Screening of known Nrf2 activators to identify CPUY192018.
• In vitro studies using macrophages from COPD patients.
• In vivo studies using cigarette smoke extract-induced COPD mouse models.

Main Results:

• CPUY192018 inhibits glycolysis and enhances antioxidative stress in COPD macrophages and mice.
• The drug disrupts Keap1-Nrf2 and Keap1-actin interactions.
• CPUY192018 boosts alveolar macrophage phagocytic function.

Conclusions:

• CPUY192018 effectively counteracts oxidative stress and reprograms metabolism in COPD.
• Nrf2 activation by CPUY192018 presents a promising therapeutic avenue for COPD patients.