Puromycin-sensitive aminopeptidase

Puromycin-sensitive aminopeptidase (PSA, encoded by NPEPPS) is a broadly specific aminopeptidase involved in proteolytic processing of peptides essential for cell growth and viability (UniProt: P55786). The enzyme plays roles in neuropeptide regulation, antigen processing for MHC class I presentation, and cytotoxic T-cell epitope trimming. PSA also degrades polyglutamine-containing peptides found in many proteins and can process tau protein.

PSA is expressed across multiple tissues and participates in both general protein catabolism and specialized immune pathways (UniProt: P55786). The enzyme's ability to digest tau from normal brain more efficiently than pathological tau suggests potential involvement in tau pathology.

PSA shows elevated levels in Alzheimer's disease brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of +0.54 across detected subcellular fractions in post-mortem TMT-proteomics analysis. This upregulation may reflect compensatory proteolytic responses to protein misfolding or accumulation characteristic of AD pathology, though the functional significance of increased PSA levels in disease progression remains to be clarified.