Gangliosides in Neurodegenerative Diseases

The main purpose of this chapter is to summarize the chief findings on ganglioside changes/interactions with some of the neurodegenerative disorders. For the latter we have focused on three diseases that have seen especially intensive study in that regard: Parkinson’s, Alzheimer’s, and Huntington’s diseases. Parkinson’s disease (PD) has received the most intensive study with revelation of systemic deficiency of GM1 in brain and all peripheral tissues that have been analyzed to date; this pointed to GM1 replacement as a promising therapy which proved only partially successful when tried for reasons that are discussed. Huntington’s disease resembles PD in also manifesting GM1 deficiency, which did, however, respond to GM1 replacement therapy – apparently due to GM1 being administered directly into the brain. Alzheimer’s disease was more complex in relation to gangliosides, with b-series (GD1b, GT1b) apparently depressed along with a-series. GM1 administered in brain appeared to induce improvement, but in a limited number of patients. We summarize studies showing why GM1 is of critical importance in neuronal function, and we also briefly point to a few additional neurological disorders in which one or more ganglioside changes have been implicated.