Beta-methylamino L-alanine
Encyclopedia
β-Methylamino-L-alanine, or BMAA, is a neurotoxin
found in the seeds of the cycad
. This non-proteinogenic amino acid (very similar to the non-essential amino acid alanine
) is produced by cyanobacteria of the genus Nostoc
that live on the plant's roots.
/parkinsonism
–dementia
complex (ALS/PDC) that has an extremely high rate of incidence among the Chamorro
people of Guam
. The Chamorro call the condition lytico-bodig
.
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.
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.
of ALS/PDC . Subsequent laboratory investigations discovered the presence of BMAA. BMAA induced severe neurotoxicity in rhesus macaques, including:
There are reports that low BMAA concentrations can selectively kill cultured
motor neurons from mouse spinal cord
s. In the motor neurons, BMAA activates AMPA
-kainate
glutamate receptor
s and boosted production of oxygen radicals.
s.
Neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...
found in the seeds of the cycad
Cycad
Cycads are seed plants typically characterized by a stout and woody trunk with a crown of large, hard and stiff, evergreen leaves. They usually have pinnate leaves. The individual plants are either all male or all female . Cycads vary in size from having a trunk that is only a few centimeters...
. This non-proteinogenic amino acid (very similar to the non-essential amino acid alanine
Alanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...
) is produced by cyanobacteria of the genus Nostoc
Nostoc
Nostoc is a genus of cyanobacteria found in a variety of environmental niches that forms colonies composed of filaments of moniliform cells in a gelatinous sheath.The name "Nostoc" was invented by Paracelsus...
that live on the plant's roots.
Neurotoxicity
BMAA is considered a possible cause of the amyotrophic lateral sclerosisAmyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
/parkinsonism
Parkinsonism
Parkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous, and diagnosis can be complex...
–dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
complex (ALS/PDC) that has an extremely high rate of incidence among the Chamorro
Chamorros
The Chamorro people, or Chamoru people, are the indigenous peoples of the Mariana Islands, which include the American territory of Guam and the United States Commonwealth of the Northern Mariana Islands in Micronesia. Today, significant Chamoru populations also exist in several U.S. states...
people of Guam
Guam
Guam is an organized, unincorporated territory of the United States located in the western Pacific Ocean. It is one of five U.S. territories with an established civilian government. Guam is listed as one of 16 Non-Self-Governing Territories by the Special Committee on Decolonization of the United...
. The Chamorro call the condition lytico-bodig
Lytico-Bodig disease
Lytico-Bodig disease, sometimes spelled Lytigo-bodig is a neurological disease of uncertain aetiology that exists in the United States territory of Guam....
.
Sources
In the 1950s, ALS/PDC prevalence ratios and death rates for Chamorro residents of Guam and RotaRota (island)
Rota also known as the "peaceful island", is the southernmost island of the United States Commonwealth of the Northern Mariana Islands and the second southernmost of the Marianas Archipelago. It lies approximately 40 miles north-northeast of the United States territory of Guam...
were 50–100 times that of developed countries, including the United States. No demonstrable heritable or viral
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
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
Cycas
Cycas is the type genus and the only genus currently recognised in the cycad family Cycadaceae. About 95 species are currently accepted. The best-known species is Cycas revoluta, widely cultivated under the name "Sago Palm" or "King Sago Palm" due to its palm-like appearance although it is not a...
circinalis) seeds in food and traditional medicine had decreased as the Chamorro population became more Americanized following World War II.
In addition to eating the seeds directly, BMAA may have found its way into human diets by way of biomagnification
Biomagnification
Biomagnification, also known as bioamplification or biological magnification, is the increase in concentration of a substance that occurs in a food chain as a consequence of:* Persistence...
. Fruit bats
Fruit Bats
Fruit Bats is an American rock band formed in 1997 in Chicago. Noted as an early entrant into the folk-rock boom of the early 2000s, the group has had many personnel changes but revolves around singer/songwriter Eric D. Johnson.-History:In 2000, Eric D...
, a Chamorro delicacy
Delicacy
A delicacy is a food item that is considered highly desirable in certain cultures. Often this is because of unusual flavors or characteristics or because it is rare....
, 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.
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 etiologyEtiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
of ALS/PDC . Subsequent laboratory investigations discovered the presence of BMAA. BMAA induced severe neurotoxicity in rhesus macaques, including:
- limb muscle atrophyAtrophyAtrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
- nonreactive degeneration of anterior horn cells
- degeneration and partial loss of pyramidal neurons of the motor cortexMotor cortexMotor cortex is a term that describes regions of the cerebral cortex involved in the planning, control, and execution of voluntary motor functions.-Anatomy of the motor cortex :The motor cortex can be divided into four main parts:...
- behavioral dysfunction
- conductionAction potentialIn physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
deficits in the central motor pathway - neuropathological changes of motor cortex Betz cellBetz cellBetz cells are pyramidal cell neurons located within the fifth layer of the grey matter in the primary motor cortex, M1. They are named after Vladimir Alekseyevich Betz, who described them in his work published in 1874. These neurons are the largest in the central nervous system, sometimes reaching...
s
There are reports that low BMAA concentrations can selectively kill cultured
Tissue culture
Tissue culture is the growth of tissues or cells separate from the organism. This is typically facilitated via use of a liquid, semi-solid, or solid growth medium, such as broth or agar...
motor neurons from mouse spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
s. In the motor neurons, BMAA activates AMPA
AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA...
-kainate
Kainate receptor
Kainate receptors, or KARs, are non-NMDA ionotropic receptors which respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a drug first isolated from red algae Digenea simplex. KARs are less well...
glutamate receptor
Glutamate receptor
Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins and as a result is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the...
s and boosted production of oxygen radicals.
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 chainFood chain
A food web depicts feeding connections in an ecological community. Ecologists can broadly lump all life forms into one of two categories called trophic levels: 1) the autotrophs, and 2) the heterotrophs...
s.