title: Mechanisms of beta-N-methylamino-L-alanine induced neurotoxicity.
abstract: Since the initial discovery that the amino acid beta-N-methylamino-L-alanine (BMAA) was a neurotoxin, a great deal has been learned about its mechanism of action. However, exactly how it causes death of motor neurons, and how its actions may interact with other neurotoxins or pathological conditions, is not well understood. The focus of study on the mechanism of BMAA toxicity has been on its action as a glutamate receptor agonist. There is evidence that BMAA has effects on all of the main types of glutamate receptors: NMDA, AMPA/kainate, and metabotropic receptors. However, recent results suggest that BMAA may also act through other mechanisms to induce neuronal death. One such action is on the cystine/glutamate antiporter (system xc(-)). Through its effect of system xc(-), BMAA can induce oxidative stress and increase extracellular glutamate. This action of BMAA provides an attractive mechanism for the multiple neurological deficits that BMAA has been implicated in inducing.
authors.affiliation: Department of Biomedical Sciences, Marquette University, 561 N. 15th Street, Milwaukee, Wisconsin 53233, USA. Doug.Lobner@marquette.edu
authors.forename: Doug
authors.initials: D
authors.lastname: Lobner
mesh_terms: D000599:Amino Acids, Diamino / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D000087522:Cyanobacteria Toxins; D003553:Cystine / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017470:Receptors, Glutamate / Q000378:metabolism
chemical_list: D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D017470:Receptors, Glutamate; C001824:beta-N-methylamino-L-alanine; D018698:Glutamic Acid; D003553:Cystine