Alpha-N-acetylgalactosaminidase (NAGA) (NAGA)

Alpha-N-acetylgalactosaminidase, commonly referred to as Nagalase, is a lysosomal enzyme (EC 3.2.1.49) encoded by the NAGA gene that catalyzes the removal of terminal alpha-N-acetylgalactosamine residues from glycoproteins and glycolipids (UniProt P17050). In healthy individuals, it is essential for the normal catabolism of glycoconjugates, and its deficiency results in Schindler disease, a rare autosomal recessive lysosomal storage disorder characterized by neurological impairment (NIH/GARD). In the context of oncology and infectious diseases, Nagalase is reported to be secreted by malignant cells and certain viruses, such as HIV and influenza, into the host's circulation (PubMed PMID: 15630446). It is hypothesized that this extracellular Nagalase deglycosylates the Vitamin D-binding protein (Gc protein), which is a precursor to the Gc-derived Macrophage Activating Factor (GcMAF), thereby preventing macrophage activation and facilitating immune evasion by the tumor or pathogen (PubMed PMID: 20976141). While serum Nagalase activity has been proposed as a biomarker for monitoring cancer progression and therapeutic efficacy, its role as a direct drug target is primarily explored through the administration of GcMAF to bypass the enzyme's inhibitory effects, though such treatments remain highly controversial and lack FDA approval.

Other names

NagalaseN-acetyl-alpha-galactosaminidaseAlpha-galactosidase B

Hydrolysis of terminal non-reducing alpha-D-N-acetylgalactosamine residues in alpha-N-acetylgalactosaminides.