Beta-methylamino L-alanine

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Neurotoxicity

BMAA is considered a possible cause of the amyotrophic lateral sclerosis/parkinsonism–dementia complex (ALS/PDC) that has an extremely high rate of incidence among the Chamorro people of Guam.^[1] The Chamorro call the condition lytico-bodig.^[2]

Sources of BMAA

In the 1950s, ALS/PDC prevalence ratios and death rates for Chamorro residents of Guam and Rota were 50–100 times that of developed countries, including the United States. No demonstrable heritable or viral factors were found for the disease, and a subsequent decline of ALS/PDC after 1955 on Guam, led to the search for responsible environmental agents. The use of cycad (Cycas circinalis) seeds in food and traditional medicine had decreased as the Chamorro population became more Americanized following World War II.^[3]

In addition to eating the seeds directly, BMAA may have found its way into human diets by way of biomagnification. Fruit bats, a Chamorro delicacy, may feed on cycad seeds and concentrate the toxin in their flesh. Three museum specimen bats, collected in Guam in the 1950s, contained hundreds of times more BMAA, gram for gram, than cycad seeds.^[2]

BMAA neurotoxic effects

Degenerative locomotor diseases had been described in animals grazing on cycad species, fueling interest in a possible link between the plant and the etiology of ALS/PDC . Subsequent laboratory investigations discovered the presence of BMAA. BMAA induced severe neurotoxicity in rhesus macaques, including:^[3]

• limb muscle atrophy
• nonreactive degeneration of anterior horn cells
• degeneration and partial loss of pyramidal neurons of the motor cortex
• behavioral dysfunction
• conduction deficits in the central motor pathway
• neuropathological changes of motor cortex Betz cells

There are reports that low BMAA concentrations can selectively kill cultured motor neurons from mouse spinal cords. In the motor neurons, BMAA activates AMPA-kainate glutamate receptors and boosted production of oxygen radicals.^[2]

Worldwide concerns

The presence of BMAA in cyanobacteria, among the most populous organisms in the world, has raised concerns that humans worldwide may be exposed to levels of BMAA that could be potentially harmful. Cyanobacteria from soil and water samples collected around the world produce BMAA, giving rise to speculative biomagnification in food chains.^[2]

References

1. ^ Cox, P.A., S.A. Banack, S.J. Murch, U. Rasmussen, G. Tien, R.R. Bidigare, J.S. Metcalf, L.F. Morrison, G.A. Codd, B. Bergman 2005. Diverse taxa of cyanobacteria produce β-N-methylamino-L-alanine, a neurotoxic amino acid. Proceedings of the National Academy of Sciences of the United States of America 102: 5074-5078. [1]
2. ^ ^{a b c d} Miller, G. July 2006. Guam's Deadly Stalker: On the Loose Worldwide? Science 28 (313): 428-431.
3. ^ ^{a b} Spencer, P.S., P.B. Nunn, J. Hugon, A.C. Ludolph, S.M. Ross, D.N. Roy, and R.C. Robertson July 1987. Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin. Science 31 (237): 517-522.