Keeping it trim: roles of neuraminidases in CNS function

Abstract

The sialylated glyconjugates (SGC) are found in abundance on the surface of brain cells, where they form a dense array of glycans mediating cell/cell and cell/protein recognition in numerous physiological and pathological processes. Metabolic genetic blocks in processing and catabolism of SGC result in development of severe storage disorders, dominated by CNS involvement including marked neuroinflammation and neurodegeneration, the pathophysiological mechanisms of which are still discussed. SGC patterns in the brain are cell and organelle-specific, dynamic and maintained by highly coordinated processes of their biosynthesis, trafficking, processing and catabolism. The changes in the composition of SGC during development and aging of the brain cannot be explained based solely on the regulation of the SGC-synthesizing enzymes, sialyltransferases, suggesting that neuraminidases (sialidases) hydrolysing the removal of terminal sialic acid residues also play an essential role. In the current review we summarize the roles of three mammalian neuraminidases: neuraminidase 1, neuraminidase 3 and neuraminidase 4 in processing brain SGC. Emerging data demonstrate that these enzymes with different, yet overlapping expression patterns, intracellular localization and substrate specificity play essential roles in the physiology of the CNS.

Subthreshold Voltage Analysis Demonstrates Neuronal Cell-Surface Sialic Acids Modulate Excitability and Network Integration

“…We speculate that the neuron uses the sialylation state of different populations of membrane biomolecules, such as gangliosides, ion channels, and receptors, to finely modulate their electrophysiological behavior. This is consistent with the presence of multiple endogenous neuraminidase enzymes in the brain that possess different substrate specificity and are actively regulated in response to electrophysiological activity (Pshezhetsky and Ashmarina, 2018). Prior studies demonstrating that blocking endogenous neuraminidase activity affects network spiking properties further support this hypothesis (Isaeva et al, 2010).…”

Control of Innate Immunity by Sialic Acids in the Nervous Tissue

“…Sialidase 3 (a membrane sialidase, also called N-acetyl-alpha-neuraminidase 3; NEU3) is encoded by the NEU3 gene and localized in the plasma membrane, while sialidase 4 (N-acetyl-alpha-neuraminidase 4; NEU4) is encoded by the NEU4 gene and displays on internal membranes. In the mouse brain, NEU1, NEU3 and NEU4 show similar expression patterns [ 69 , 70 ]. Moreover, these sialidases are active against different but overlapping sialylated glycoconjugates.…”

Metabolite Profile Changes in Different Regions of Rat Brain Affected by Ephedra sinica

“…Sialic acid, as a class amino sugar, is usually located at the end of the sugar chain on the cell membrane. In the CNS, neuraminic acid mainly combines with sphingolipid to form ganglioside, which plays an important role in neurogenesis, synaptic plasticity, and nerve impulse transmission [46]. Compared with CG, the concentration of neuraminic acid was significantly increased in 6 brain regions after administration, especially in the cortex, hypothalamus, and oblongata (Figure 4), which suggested that EP markedly changed the amino sugar metabolism in the three regions.…”