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2014 ; 94
(2
): 461-518
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Sialic acids in the brain: gangliosides and polysialic acid in nervous system
development, stability, disease, and regeneration
#MMPMID24692354
Schnaar RL
; Gerardy-Schahn R
; Hildebrandt H
Physiol Rev
2014[Apr]; 94
(2
): 461-518
PMID24692354
show ga
Every cell in nature carries a rich surface coat of glycans, its glycocalyx,
which constitutes the cell's interface with its environment. In eukaryotes, the
glycocalyx is composed of glycolipids, glycoproteins, and proteoglycans, the
compositions of which vary among different tissues and cell types. Many of the
linear and branched glycans on cell surface glycoproteins and glycolipids of
vertebrates are terminated with sialic acids, nine-carbon sugars with a
carboxylic acid, a glycerol side-chain, and an N-acyl group that, along with
their display at the outmost end of cell surface glycans, provide for varied
molecular interactions. Among their functions, sialic acids regulate cell-cell
interactions, modulate the activities of their glycoprotein and glycolipid
scaffolds as well as other cell surface molecules, and are receptors for
pathogens and toxins. In the brain, two families of sialoglycans are of
particular interest: gangliosides and polysialic acid. Gangliosides, sialylated
glycosphingolipids, are the most abundant sialoglycans of nerve cells. Mouse
genetic studies and human disorders of ganglioside metabolism implicate
gangliosides in axon-myelin interactions, axon stability, axon regeneration, and
the modulation of nerve cell excitability. Polysialic acid is a unique
homopolymer that reaches >90 sialic acid residues attached to select
glycoproteins, especially the neural cell adhesion molecule in the brain.
Molecular, cellular, and genetic studies implicate polysialic acid in the control
of cell-cell and cell-matrix interactions, intermolecular interactions at cell
surfaces, and interactions with other molecules in the cellular environment.
Polysialic acid is essential for appropriate brain development, and polymorphisms
in the human genes responsible for polysialic acid biosynthesis are associated
with psychiatric disorders including schizophrenia, autism, and bipolar disorder.
Polysialic acid also appears to play a role in adult brain plasticity, including
regeneration. Together, vertebrate brain sialoglycans are key regulatory
components that contribute to proper development, maintenance, and health of the
nervous system.