Neurobiology Meets Glycosciences - The Sugar Code - page 503

gangliotetraose gangliosides (Figure 30.2) characteristic of brain [13]. However,
these are not the major gangliosides of the PNS, that being the N - acetylglucos-
amine - containing species 3 ′ LM1 (NeuAc α 2,3Gal β 1,4GlcNAc β 1,3Gal β 1,4Glc β 1,1 ′

Cer). This ganglioside in peripheral nerves occurs primarily in myelin and has not
been detected in CNS myelin. Interestingly, the most abundant acidic GSL in the
human PNS is not a ganglioside, but rather inositolphosphoryl galactoslylce-
ramide, whose acidity is due to phosphate rather than Neu5Ac. Anti- GSL antibod-
ies are directly involved in the pathogenesis of Guillain- Barr é syndrome and
related peripheral neuropathies [14]. These are autoantibodies directed against
some 20 or more endogenous GSLs, most of which are gangliosides of the PNS.
The high antibody titers in these patients are closely associated with specifi c ante-
cedent infections, such as Campylobacter jejuni and cytomegalovirus. The mecha-
nism has been proposed to involve molecular mimicry, based on the fact that
lipopolysaccharides from these microorganisms contain structural components
that closely resemble the terminal carbohydrate structures of the peripheral GSLs.
Clinical symptoms appear to require the lipopolysaccharide entity, since anti-GSL
antibody formation via direct injection of gangliosides into humans or animals is
usually not accompanied by Guillain- Barr é syndrome - like symptoms. In addition
to gangliosides, peripheral nerves also contain sulfated GSLs that can become
targets of molecular mimicry, the primary example being sulfoglucuronosyl para-
globoside containing sulfated glucuronic acid: - SO 3 - GlcA β 1,3Gal β 1,4GlcNAc β 1,3

Gal Cer. The terminal carbohydrates comprise the human natural

killer (HNK)-1 epitope (for structural depiction, please see Figure 1.7c ; see also
below). Having reviewed the structural and metabolic features of these GSLs, we
now survey what is known of their functional behavior in the nervous system.

β 1,4Glc β 1,1 ′

30.5
Ganglioside Functional Activities

Numerous studies have documented a wide variety of neurotrophic, neuroprotec-
tive properties of GM1 and other gangliosides, many of these involving application
of exogenous ganglioside in vivo or in vitro [15]. Although in some cases these
turned out to represent nonspecifi c perturbations rather than refl ections of true
physiological function, the biological results were often signifi cant (see Info Box
1). Among several examples was GM1 rescue of substantia nigra dopaminergic
neurons in mice subjected to 1- methyl - 4 - phenyl - 1,2,3,6 - tetrahydropyridine -
a model of Parkinson's disease [16]. A clearer picture of physiological function is
coming into focus with the newer emphasis on specifi c molecular mechanisms of
endogenous gangliosides, these often involving direct association between gan-
glioside and protein. The main locus of most gangliosides is the plasma mem-
brane where, in the case of neurons, they make a major contribution to the
carbohydrate-rich glycocalyx that forms the interface for cellular interactions.
Within that matrix the oligosaccharide chains of gangliosides (and GSLs generally)
are relatively close to the cell surface and thus well situated for cis - interactions with