Histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA)-mediated correction of α1-antitrypsin deficiency

Abstract

Background:α1-Antitrypsin (α1AT) deficiency (α1ATD) is a consequence of defective folding, trafficking, and secretion of α1AT. Results: SAHA restores the secretion of an active form of Z-α1AT in part through a calnexin-and HDAC7-sensitive dependent mechanism(s). Conclusion: SAHA may represent a potential therapeutic approach for α1ATD. Significance: SAHA is a regulator of the proteostasis biology of Z-α1AT, favoring export of a functional form to serum. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.