Disease relevance of L-Bmaa

• L-Cysteine is naturally present in the human brain and in the environment, and is much more powerful than beta-N-methylamino-L-alanine, a bicarbonate-dependent excitotoxin, which has been implicated in an adult neurodegenerative disorder endemic to Guam [1].
• We report here that a single neurotoxin, beta-N-methylamino-L-alanine, may be produced by all known groups of cyanobacteria, including cyanobacterial symbionts and free-living cyanobacteria [2].
• The present study is concerned with the hypothetical toxicity of beta-N-methylamino-l-alanine (BMAA), a compound that has been hypothesized to produce amyotrophic lateral sclerosis/Parkinson-dementia complex [3].
• Plant amino acids beta-N-oxalylamino-L-alanine (L-BOAA, present in Lathyrus sativus) and beta-N-methylamino-L-alanine (L-BMAA, present in Cycas circinalis) have been implicated in the pathogenesis of human neurological disorders lathyrism and amyotrophic lateral sclerosis-Parkinson's dementia complex of Guam (ALS-PD), respectively [4].
• Motor system disease is induced in cynomolgus monkeys by feeding them beta-N-methylamino-L-alanine (BMAA), an amino acid present in cycad seeds [5].

High impact information on L-Bmaa

• Glutamate, beta-N-methylamino-L-alanine, and (1S,3R)-aminocyclopentane-1,3-dicarboxylic acid all caused concentration-dependent cerebellar granule cell death over a 24-h exposure period [6].
• Facilitated transport of the neurotoxin, beta-N-methylamino-L-alanine, across the blood-brain barrier [7].
• Among the excitatory amino acids tested, only glutamate (1-10 mM), quisqualate (1 mM) and, with less extent, beta-N-methylamino-L-alanine (10 mM) induced a significant reduction of cell survival [8].
• beta-N-Methylamino-L-alanine (BMAA) stimulated the hydrolysis of polyphosphoinositides (PPI) in hippocampal slices prepared from 8-day old rats [9].
• We have investigated the effects of serum from patients with motor neurone disease (MND) and of the plant-derived excitotoxin beta-N-methylamino-L-alanine (L-BMAA) on thyrotrophin-releasing hormone (TRH) and somatostatin (SS) production by fetal rat brainstem cell cultures [10].

Biological context of L-Bmaa

• We investigated the effect of beta-N-methylamino-L-alanine (L-BMAA) on input membrane resistance of leech Retzius nerve cells and the effect of the same substance on the membrane potential in the presence of 20 mM bicarbonate [11].
• Rats receiving intracerebroventricular administration of 10 nanomoles of L-BMAA (beta-N-methylamino-L-alanine) were found to grow more slowly and contain less brain L-(3H) glutamate binding sites than rats receiving injection of phosphate-buffered saline (PBS) [12].

Anatomical context of L-Bmaa

• beta-N-Oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) are chemically related excitant amino acids isolated from the seed of Lathyrus sativus (BOAA) and Cycas circinalis (BMAA), consumption of which has been linked to lathyrism (an upper motor neuron disorder) and Guam amyotrophic lateral sclerosis (ALS), respectively [13].

Associations of L-Bmaa with other chemical compounds

• Determination of beta-N-methylamino-L-alanine (BMAA) in plant (Cycas circinalis L.) and animal tissue by precolumn derivatization with 9-fluorenylmethyl chloroformate (FMOC) and reversed-phase high-performance liquid chromatography [14].

Analytical, diagnostic and therapeutic context of L-Bmaa

• Traditionally processed cycad flours (n = 17) obtained from Chamorro residents of Guam and the adjacent island of Rota at risk for neurodegenerative disease were extracted and analyzed by high-performance liquid chromatography for content of beta-N-methylamino-L-alanine (BMAA) and methyl-azoxymethanol beta-D-glucoside (cycasin) [15].

References