Protein phosphatase 2A activators under investigation for smoking-related chronic obstructive pulmonary disease and related disorders.

Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by progressive inflammation during therapy. Cystic fibrosis (CF), alpha-one antitrypsin deficiency (AATD), and non-CF bronchiectasis are also chronic respiratory disorders with inflammation and progression that share many similarities with COPD. Therefore, various anti-inflammatory approaches are currently being investigated, and protein phosphatase 2A (PP2A) activators may represent one such approach.

Areas covered: Systematic review of papers published from 2000-to date on the anti-inflammatory role of endogenous PP2A, the consequences of its inhibition by smoking, and the beneficial effects of its activation in COPD.

Expert opinion: PP2A activation is a plausible therapeutic approach in COPD and related disorders, such as CF, AATD, and non-CF bronchiectasis, although the available evidence is still mostly experimental. Metformin repurposing and consideration of inhalation for some of the molecules discussed in this study are promising approaches.