Cathepsin A (CTSA) (CTSA)

Cathepsin A (CTSA), also known as Protective Protein/Cathepsin A (PPCA), is a multifunctional lysosomal serine carboxypeptidase (UniProt: P10619). Its primary physiological role is to form a high-molecular-weight complex with beta-galactosidase and neuraminidase 1, protecting them from premature degradation within the lysosome (PubMed: 25130630). In the context of Alzheimer's disease, PPCA has been identified as a potent amyloid-beta (Aβ) degrading enzyme (PubMed: 22833674). Overexpression of PPCA, often explored via gene therapy, facilitates the proteolytic clearance of Aβ42 aggregates, thereby reducing plaque burden and associated neurotoxicity in preclinical models. This makes it a promising therapeutic target for enhancing the brain's endogenous capacity to eliminate pathogenic protein aggregates. The enzyme specifically targets the C-terminus of the Aβ peptide, converting it into smaller, non-toxic fragments. While its upregulation may be a natural compensatory response in the early stages of neurodegeneration, therapeutic strategies aim to maximize this effect to halt disease progression.

Other names

Protective Protein/Cathepsin APPCALysosomal carboxypeptidase AHPP1GSLBeta-galactosidase protective protein

Cathepsin A acts as a carboxypeptidase that cleaves the C-terminal residues of Amyloid-beta 1-42, converting it into shorter, less aggregation-prone fragments, thereby reducing the formation of amyloid plaques.