Community Research and Development Information Service - CORDIS

Biological function of sialidase enzymes

European researchers set out to clarify the biological functions of mammalian sialidases, enzymes implicated in neurodegenerative disorders.
Biological function of sialidase enzymes
Sialidases or neuraminidases are a family of hydrolytic enzymes that remove the sialic acid carbohydrate modifications from glycolipids, glycoproteins and oligosaccharides. To date, four mammalian sialidases have been cloned, namely a lysosomal form (Neu1), a cytosolic form (Neu2), a plasma membrane-associated form (Neu3) and a lysosomal/mitochondrial form (Neu4).

In humans, the highest sialic acid concentration is encountered in the brain, where they function in neuronal transmission. A role for sialic acid on maintaining a negative charge on the surface of cells and facilitating fluid uptake has been proposed.

Scientists on the EU-funded CATABOLIC SIALIDASES (Understanding the roles of mammalian sialidases in glycolipid catabolism) project were interested in defining the role of mammalian sialidase Neu1 in glycolipid degradation. For this purpose, they generated mice knockout in Neu1 and crossed them with animals lacking hexosaminidase A (HEXA), the gene implicated in Tay-Sachs disease. Lack of HEXA decreases the hydrolysis of GM2 gangliosides, which accumulate in neurons and cause neurodegeneration.

In addition, scientists generated animals lacking HexA, Neu1 and Neu4 and analysed the brain gangliosides by thin layer chromatography. They observed an altered ganglioside pattern in double knockout as well as triple knockout mice compared to single knockout (HexA, Neu4 or Neu1) mice. Further biochemical analysis by mass spectrometry, immunohistochemical and molecular biological analyses in brain tissue from those animals revealed interesting observations.

Overall, the CATABOLIC SIALIDASES project came a step closer to defining the functional impact of sialidases on the complex physiological and cellular processes. Uncovering the biological significance of sialidase-susceptible sialic acids on glycoproteins and glycolipids, should prove useful in designing interventions against sialidase-associated diseases.

Related information


Sialidase, neuraminidase, Neu1, brain, HEXA, Tay-Sachs disease, GM2 ganglioside
Follow us on: RSS Facebook Twitter YouTube Managed by the EU Publications Office Top