Mammalian neuraminidase (NEU) (NEU)

Mammalian neuraminidases, also known as sialidases, are a family of four enzymes (NEU1, NEU2, NEU3, and NEU4) that catalyze the removal of terminal sialic acid residues from glycoproteins and glycolipids (Miyagi & Yamaguchi, 2012, Glycobiology). These enzymes are localized in distinct cellular compartments—lysosomes, cytosol, and plasma membranes—where they regulate critical processes such as cell signaling, immune response, and lysosomal degradation (UniProt: Q99519, Q9UQG6). NEU1 is the most widely expressed isoform and is essential for lysosomal function; its deficiency leads to the lysosomal storage disorder sialidosis (NIH: Genetic and Rare Diseases Information Center). NEU3 is primarily associated with the plasma membrane and is frequently upregulated in various cancers, where it modulates ganglioside-mediated signaling to promote tumor progression (PubMed: 22510516). In recent years, these enzymes have emerged as therapeutic targets for conditions including pulmonary fibrosis, atherosclerosis, and various malignancies (PubMed: 30107084). While clinical neuraminidase inhibitors like oseltamivir were developed for influenza, they demonstrate some cross-reactivity with mammalian isoforms, leading to research into more selective inhibitors for human disease applications (PubChem: CID 65028). This cross-reactivity has led to research into repurposing these drugs or developing new, highly selective inhibitors to treat chronic human conditions without affecting viral defense (PubMed: 25663131). Consequently, mammalian neuraminidases represent a versatile class of therapeutic targets with applications spanning oncology, immunology, and metabolic medicine.

Other names

SialidaseExo-alpha-sialidaseN-acetylneuraminate glycohydrolaseNeuraminidase

Competitive inhibition of the sialidase enzyme, preventing the hydrolytic cleavage of terminal sialic acid residues from glycoproteins and glycolipids, thereby modulating cell surface signaling and lysosomal catabolism.