PARADOXICAL RESPONSES TO NEUROTOXIC STERYL GLYCOSIDES: INSIGHTS FROM A CELLULAR MODEL OF ALSPDC.

The causes of many sporadic neurodegenerative diseases remain unknown making prevention difficult, if not impossible. One clue comes from the study of amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC) of Guam which shares many similarities with amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease seen in other parts of the world. This disorder may provide a unique opportunity to study the cause and progression of neurodegenerative diseases. Epidemiological and experimental findings indicate that dietary consumption of cycad seeds is an underlying cause of ALS-PDC. Our laboratory provided evidence that a family of compounds called steryl glycosides are the active ingredients that may be responsible for producing the neurodegenerative outcome in ALS-PDC. Here, we review some of our work on the chronic toxicity of steryl glycosides in neuronal cells maintained in cell culture and in an in vivo mouse model. The current studies indicate some mechanisms about how neuronal cells respond to this class of toxins.