Alpha-1 antitrypsin (A1AT) (A1AT)

Alpha-1 antitrypsin (A1AT), encoded by the SERPINA1 gene, is a member of the serpin superfamily that functions as a major inhibitor of serine proteases, particularly neutrophil elastase [1][2]. Produced primarily in the liver, A1AT is secreted into the systemic circulation to protect the delicate alveolar tissues of the lungs from proteolytic damage during inflammatory responses [2]. In individuals with Alpha-1 antitrypsin deficiency (AATD), mutations such as the PiZ variant (Glu342Lys) cause the protein to misfold and form insoluble polymers within the endoplasmic reticulum of hepatocytes [1][3]. This mechanism leads to a dual disease state: liver injury due to the accumulation of toxic polymers and progressive lung destruction (emphysema) due to the lack of circulating A1AT [3][4]. Current therapeutic strategies include augmentation therapy with plasma-derived A1AT to restore lung protection, while investigational therapies like RNA interference (RNAi) and gene editing (e.g., base editing) aim to reduce the production of or correct the mutated endogenous gene to prevent liver pathology [5][6].

Other names

Serpin family A member 1SERPINA1Alpha-1-proteinase inhibitorAATProtease inhibitor 1

Therapeutic strategies include protein augmentation to restore serum levels, RNA interference (RNAi) to silence the production of toxic mutant proteins in the liver, and gene editing or small molecule correctors to prevent protein misfolding and polymerization.