| Structure of BMAA and Glutamate|
Vega and Bell
identified a new bioactive compound from the species Cycas micronesia
(as C. circinalis) found in Guam. With this discovery the focus of the
search for a cycad neurotoxin shifted from cycasin to the new compound, BMAA (B-methylamino-L-alanine).
BMAA is a non protein amino acid and is found in all genera but at highest
concentrations in the genus Cycas, which is found in Guam, Kii
Peninsula and New Guinea. It's chemical structure showed tantalizing similarities
to BOAA, the neurotoxin from the chick pea.
|Function of the Glutamate receptor|
Diagram by Eric Brenner
BMAA is thought to be weakly excitotoxic to neurons by acting at the
glutamate receptor as an agonist
(Marini et al. 1992).
It works by mimicking the effect of the neurotransmitter glutamate which is naturally
present in the brain. Although glutamate is an important signaling molecule in the brain
in certain circumstances, it can have excitotoxic effects.
Finally in 1987
Spencer et al. 1987
were able to elicit neurological symptoms by feeding primates BMAA. However these
experiments were soon criticized as inconclusive
(Garruto et al. 1988).
mainly because very high doses of BMAA had been used. Also, the symptoms and
pathology produced in the test monkeys were not exactly the same as those observed
in the human disease.
If BMAA is involved and as has been shown to be a relatively weak toxin,
how is it possible to ingest enough plant material to provide toxic levels of BMAA?
Cycad seeds contain low concentrations of BMAA
and up to 80% of this was removed after processing
(Duncan letter to Lancet).
Once again, in the lab BMAA seemed an excellent candidate in the search
for a causative of ALS-PD but in real life there were many problems with this hypothesis.