Meta-Biol

• Pathways

NEU1 Sialidase 1 (NEU1, neuraminidase, receptor-destroying enzyme, RDE) normally hydrolyses N-acetylneuraminic acid (Neu5Ac) from glycoconjugates with alpha2,3-, alpha2,6- or alpha2,8-linked terminal sialated residues in the lysosomal lumen, a step in the degradation process of glycoproteins and gangliosides. NEU1 is active in a multienzyme complex comprising cathepsin A protective protein (CTSA) and beta-galactosidase (Bonten et al. 1996, Rudenko et al. 1995). Defects in NEU1 cause Sialidosis (MIM:256550), a lysosomal storage disorder manifesting as type I (late-onset) or type II (earlier-onset) (Bonten et al. 1996). Generally, patients with the more severe type II disease have catalytically inactive enzymes whereas patients with the milder type I disease have some residual activity. Mutations causing the severest type II disease include E377*, L303P, W29*, R225P and W23* (Bonten et al. 1996, Pshezhetsky et al. 1997, Sergi et al. 2001, Pattison et al. 2004).