sialidasesNEU1

Sialidases, or neuraminidases, are enzymes that hydrolyze sialic acid residues from glycoproteins, glycolipids, and oligosaccharides. In humans, four active sialidases are encoded by NEU1, NEU2, NEU3, and NEU4, with NEU1 designated as neuraminidase 1. NEU1 is primarily localized to lysosomes where it participates in the degradation of sialylated substrates, contributing to glycoprotein catabolism and the turnover of cell-surface glycoproteins.

Biochemical properties of NEU1 include its role as an acid hydrolase with optimal activity at acidic pH found in lysosomes. NEU1 functions in a multiprotein lysosomal complex that includes protective protein cathepsin A (PPCA) and β-galactosidase (GLB1). PPCA acts as a chaperone, stabilizing NEU1 and enabling proper lysosomal function; the NEU1-PPCA-GLB1 complex coordinates the breakdown of sialylated substrates released from glycoproteins and glycolipids.

Substrates and specificity: NEU1 preferentially acts on sialylated glycoproteins, with comparatively lower activity toward certain glycolipids. It removes terminal sialic acids linked by α2-3, α2-6, and α2-8 linkages, releasing free N-acetylneuraminic acid (sialic acid).

Genetic and clinical aspects: Mutations in NEU1 cause sialidosis, a lysosomal storage disorder. Sialidosis type I is typically milder, presenting with myoclonus and cherry-red retinal spots, while type II is more severe with dysmorphic features and multi-organ involvement. The disease reflects lysosomal accumulation of sialoglycoproteins due to deficient NEU1 activity.

Research and therapeutic context: NEU1 is a focus in studies of lysosomal biology, glycoprotein turnover, and certain immune processes. While therapeutic approaches such as enzyme replacement or gene therapy are explored in models, there are no NEU1-approved therapies as of now.