Neuronal Functions of Gangliosides

 1. Neurotrophic effects
The finding that gangliosides enhance neuronal differentiation originated from the observation that meganeurites, abnormally developed neuronal processes, occurred in hereditary GM1 gangliosidosis. Since then the neurite extension effects of gangliosides have been examined in in vitro and in vivo systems. The latest reports indicate some mechanisms for expressing the neurotrophic effects of gangliosides. (a) Mutoh et al. (Ref. 1) revealed that ganglioside GM1 cooperates with NGF receptor to regulate the signal transduction. (b) Ledeenユs group (Ref. 2) found the occurrence of gangliosides in nucleus, suggesting the possible involvement of gangliosides in gene expression.

2. Neuronal functions
Based on the fact that gangliosides are enriched in the nervous system, they have been speculated to participate in neuronal functions. Even after many studies, however substantial evidence for this has not yet been obtained. Lately, some new findings have shed light on the approach to neuronal functions. (a) The first report that gangliosides might facilitate long-term potentiation, LTP, as a molecular mechanism of learning and memory was the result of Seifertユs group (1985). There have been several reports supporting or denying the ganglioside effect since then. A collaborative work of Kato (Yamagata University) and Ando (Tokyo Metropolitan Institute of Gerontology) has provided a definite answer, regarding the facilitating effects of gangliosides on LTP (Ref. 3)(Fig.1). (b) Cholinergic specific gangliosiosides named Chol-1a were isolated and characterized by Andoユs group (1992). This was taken as a physiologically meaningful finding indicating that specific gangliosides may be involved in cholinergic functions. Molecular mechanisms underlying neuronal modulation by Chol-1a are now under investigation. (c) Studies using ganglioside synthase-knock-out mice have started to reveal the ganglioside functions. Since Furukawa et al. (Ref. 4) established GM2-knock- out mice, relevant neural functional defects would be expected to be found.

Fig : Effect of ganglioside GQ1b on the ling-term potentiation (LTP)(Ref.3)
LTP was not formed in low-calcium ion by tetanic stimulation (T)(A),
but remarkably formed when incubated with GQ1b (B).

3. Neural diseases and therapeutic possibility
Senile dementia of the Alzheimer type (SDAT) is known as a major degenerative disease in which severe progressive neuronal cell losses occur. According to the idea that gangliosides may effectively act on SDAT, therapeutic trials have been reported (Ref.5) Gangliosides are also reported to suppress clinical symptoms in animal models of Parkinsonユs disease (Ref. 6).
Susumu Ando
(Department of Biomembrane,
Tokyo Metropolitan Institute of Gerontology)
References (1) Mutoh T, Tokuda A, Miyadai T, Hamaguchi M, Fujiki N : Ganglioside GM1 binds to the Trk protein and regulates receptor function. Proc. Natl. Acad. Sci. USA, 92, 5087-5091, 1995
(2) Kozireski-Chuback D, Wu G, Ledeen RW : Upregulation of nuclear GM1 accompanies axon-like, but not dendrite-like, outgrowth in NG108-15 cells. J. Neurosci. Res. 55, 107-118, 1999
(3) Furuse H, Waki H, Kaneko K, Fujii S, Miura M, Sasaki H, Ito K,Kato H, Ando S : Effect of the mono- and tetra-sialogangliosides, GM1 and GQ1b, on long-term potentiation in the CA1 hippocampal neurons of the guinea pig. Exp. Brain Res. 123, 307-314, 1998
(4) Takamiya K, Yamamoto A, Furukawa K, Yamashiro S, Shin M, Okada M, Fukumoto S, Haraguchi M, Takeda N, Fujimura K, Sakae M, Kishikawa M, Shiku H, Furukawa K, Aizawa S : Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system. Proc. Natl. Acad. Sci. USA, 93, 10662-10667, 1996
(5) Svennerholm L, Life Sci., 55, 2125, 1994
(6) Schneider JS et al, J. Neurosci. Res, 42, 117-123, 1995
Jun. 15, 1999

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