neuraminidases

Neuraminidases, also known as sialidases, are enzymes that catalyze the cleavage of sialic acid residues from glycoproteins and glycolipids. They hydrolyze various linkages between sialic acid and underlying sugars, including alpha-2,3, alpha-2,6, and alpha-2,8 linkages. Neuraminidases are found across many organisms, including viruses, bacteria, fungi, plants, and animals, and they play diverse roles in physiology and pathogenesis.

In humans, four genes encode neuraminidases: NEU1, NEU2, NEU3, and NEU4. NEU1 is primarily lysosomal and participates in catabolism of desialylated glycoconjugates; NEU2 is a cytosolic enzyme with broader substrate access; NEU3 associates with the plasma membrane and desialylates glycosphingolipids, influencing signaling; NEU4 localizes to lysosomes and mitochondria and can desialylate a range of substrates. Dysfunctions in these enzymes are linked to human disease, such as sialidoses and altered cell signaling.

Viral neuraminidases, most notably those of influenza viruses, facilitate viral spread by cleaving sialic acid from host receptors, enabling newly formed virions to detach from the cell surface. They are commonly homotetramers and are a target for antiviral therapy. Bacterial and fungal sialidases contribute to pathogenesis by exposing underlying sugars in mucus, aiding adherence, and providing a source of carbon and nitrogen.

Clinical relevance includes neuraminidase inhibitors (for example, oseltamivir, zanamivir, and peramivir), which block influenza neuraminidase to limit viral replication and release. Resistance can arise through mutations in the neuraminidase gene. Neuraminidases also serve as research tools in glycobiology and in studies of host–pathogen interactions.