Natural products restore function in alpha-1-antitrypsin deficiency
Misfolding of alpha-1 antitrypsin (AAT) variants results in gain-of-toxic aggregation in the liver and loss of monomer activity in the lung leading to chronic obstructive pulmonary disease (COPD).
Using high-throughput screening (HTS) and Gaussian process (GP)-based machine learning, the researchers identified a dietary source bioactive product, phenethyl isothiocyanate (PEITC).
PEITC is highly enriched in cruciferous vegetables, including watercress and broccoli, which improves the level of monomer secretion and neutrophil elastase (NE) inhibitory activity of AAT-Z through the endoplasmic reticulum (ER) redox sensor protein disulfide isomerase (PDI) A4 (PDIA4).
PEITC restores function in alpha-1 antitrypsin deficiency (AATD) at residue-by-residue resolution by adjusting cellular redox status.
https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(24)00688-8
