Gangliosides and Modulation of Neuronal Functions (Nato ASI Subseries H:, 7, Band 7)

The NATO Advanced Research Workshop on "Gangliosides and Modu- lation of Neuronal Functions" was held at the University of Stutt- gart-Hohenheim, Federal Republic of Germany, on October 20 - 24, 1986. About 70 participants from 10 countries presented papers on a wide range of topics all concerning the ganglioside theme. The content of the workshop consisted of the following chap- ters: (1) Fundamentals for research on function of gangliosides; (2) Brain ganglioside metabolism; (3) Cell specific distribution and differentiation-related ex- pression of brain gangliosides; (4) Gangliosides and neuronal plasticity; (5) Bio-medical potential of exogenous ganglioside application on neuronal function; and (6) Critical assessments on aspects of ganglioside therapy. The aim of the workshop was to sum up and discuss the present knowledge in the respective fields. Despite intensive research on gangliosides ever since Ernst Klenk discovered them in 1936, the biological function of. these amphiphilic, "sphinx-like" glycosphingo- lipids remains elusive. Over the past few years, several thousands of articles on gangliosides have been published demonstrating very special properties of these glycolipids and their possible in- volvement in diverse biological phenomena. As far as we know up to the present time, these properties may be due to particular physico-chemical attributes of these compounds, especially in com- bination with calcium. The results obtained so far have shed light not only on pos- sible functional roles of gangliosides with regard to cellular induction and organization, but have also unexpectedly opened up VI a whole new field of therapeutic applications for these compounds.

Section I: Fundamentals for Research on Function of Gangliosides.- History of ganglioside research.- Fundamentals of the biological properties of sialic acids.- Fundamentals of ganglioside structure.- Fundamentals of structural analysis of glycosphingolipids by proton nuclear magnetic resonance spectroscopy.- Fundamentals of the application of MS and NMR in the study of ganglioside structure.- Computer predictions of glycosphingolipid conformation.- Fundamentals of physico-chemical properties of gangliosides in solution.- Fundamentals of physico-chemistry of glycolipids in membranes.- Peculiarities of ganglioside Ca2+-interactions.- Isolation and analysis of gangliosides with 0-acetylated sialic acids.- Up-to-date chromatography of gangliosides.- The use of GM1 alkaline hydrolysis products for the preparation of ganglioside molecular species and ganglio-side derivatives (Abstract).- Pyrene-labeled gangliosides: micellar properties in aqueous solution, lateral diffusion and thermotropic behaviour in phosphatidylcholine bilayer (Abstract).- Influence of Ca2+ and temperature changes on the surface requirement of gangliosides and phospholipids in monolayers (Abstract).- Stability of ganglioside monolayers at a liquid/liquid interface. A polarographic study of the Ca2+-effect (Abstract).- Summary of Section I.- Section II: Brain Ganqlioside Metabolism.- Fundamentals of brain ganglioside biosynthesis.- In vivo distribution and metabolism of exogenous gangliosides.- In vitro incorporation and metabolism of gangliosides.- Fundamentals of ganglioside catabolism.- Gangliosides: Biosynthesis, transport and location in the plasma membrane.- Fundamentals of neuronal transport of gangliosides. Functional implications.- Fundamentals of genetic control of gangliosides: The enigma of carbohydrate chain diversity in glycosphingolipids.- Genetic regulation of ganglioside expression.- Drug induced alterations of ganglioside biosynthesis.- Inhibition of GM2 and GD3 synthase by end-product gangliosides in vitro (Abstract).- Substrate specifity of GM2 synthase and GD3 synthase of Golgi vesicles derived from rat liver (Abstract).- Effect of veratrine or ganglioside biosynthesis in cerebellar cultures (Abstract).- New aspects in the determination of endogenous membrane-bound sialidase in the CNS, using 4-MU-NeuAc as an exogenous artificial substrate (Abstract).- Axonal transport of intraocularly injected (3H-Sph)-GD1a and (3H-Sph)-GM1 (Abstract).- Functionally distinct oncogenes differently regulate cellular expression of gangliosides (Abstract).- Summary of Section II.- Section III: Cell specific distribution and differentiation-related expression of brain gangliosides.- Phylogeny of vertebrate brain gangliosides.- Insects: Animals without gangliosides — Preliminary data.- Pre-organ glycolipids and pre-brain gangliosides.- Ontogeny of vertebrate brain gangliosides.- Brain gangliosides and neurological mutants.- Gangliosides as autoantigens and differentiation antigens.- Monoclonal antibodies against gangliosides.- Glioma-associated gangliosides.- Treatment of patients with neuroectodermal tumors by monoclonal ganglioside antibodies.- Brain gangliosides in birds and mammals with altrical versus precocial type of development (Abstract).- Determination of Chol-1 antigen in human brain and neuroblastoma tumor (Abstract).- Antigenicity of gangliosides (Abstract).- Summary of Section III.- Section IV: Gangliosides and neuronal plasticity.- Ganglioside-mediated modulation of growth factor receptor function and cell adhesion.- Modulation of neuronotrophic factor action by exogenous gangliosides.- The neuritogenic effect of gangliosides in cell cultures.- Brain gangliosides, bio-electrical activity and post-stimulation effects.- Gangliosides and neuronal plasticity in the rat hippocampus.- Gangliosides as differential modulators of protein phosphorylation (Abstract).- Gangliosides and neuropathy.- Voltage clamp analysis of exogenous ganglioside (GM1)application on Aplysia neurons (Abstract).- Histo-autoradiographic investigations on the incorporation of 14C-N-acetyl-mannosamine into the brain of fat dormice (Glis glis) adapted to different temperatures (Abstract).- Immunohistochemical localization of GM1 ganglioside in human skeletal muscle in neuropathies and myopathies (Abstract).- Summary of Section IV.- Section V: Bio-medical potential of exogenous ganglioside-application on neuronal functions.- Nerve cell cultures as tool for research on ganglioside function (Abstract).- Gangliosides and functional recovery of injured nervous systems (Abstract).- Clinical aspects on bio-medical potential of exogenous ganglioside application.- Present state of clinical experience of ganglioside application in man.- Uptake of exogenous gangliosides by the CNS?.- Effect of gangliosides on nerve conduction velocity during diabetic neuropathy in the rat (Abstract).- GM1 ganglioside injections increase axon sprouting in the retinotectal system of the hamster (Abstract).- Summary of Section V.- Section VI: Round Table Discussion.- Critical assessment on the transferability of in vitro-results to the in vivo-situation. An attempt to delimite the effects and the action mechanisms of exogenous gangliosides.- Assessment of the significance of clinical tests in general.- Summary of Section VI: Critical Assessment of Aspects of Ganglioside Therapie.- VII: List of Participants.- VIII: Contributor Index.- IX: Subject Index.