The medicinal and food use of seed from the cycad plant (Cycas spp.), which contains the
neurotoxin cycasin, is a proposed etiological factor for
amyotrophic lateral sclerosis/
Parkinsonism dementia complex (ALS/PDC), a prototypical
neurodegenerative disease found in the western Pacific.
Cycasin, the beta-D-
glucoside of
methylazoxymethanol might enter neurons and other cells via a
glucose transporter. Since the intestinal brush-border Na+/
glucose cotransporter plays a major role in the absorption of
monosaccharides, the following studies were conducted to determine if
cycasin, the beta-D-
glucoside of
methylazoxymethanol, is a substrate for the transporter. We measured the ability of
cycasin to (i) inhibit Na+/
glucose uptake into rabbit intestinal brush-border membrane vesicles, and (ii) to generate current by the cloned Na+/
glucose cotransporter (SGLT1) expressed in Xenopus laevis oocytes. The results show that
cycasin inhibits Na(+)-dependent
sugar transport in the vesicles, and
cycasin generates
phlorizin-sensitive currents in oocytes. We conclude that
cycasin is a substrate for the intestinal brush-border Na+/
glucose cotransporter, albeit with a lower affinity than
D-glucose. This suggests that
cycasin may be absorbed from the gut lumen by the cotransporter, and as a result either
cycasin or the aglycone is presented to the blood-brain barrier for uptake into the brain.