Mechanisms of β-N-methylamino-L-alanine induced neurotoxicity

摘要

Since the initial discovery that the amino acid β-N-methylamino-L-alanine (BMAA) was a neurotoxin, a great deal hasbeen learned about its mechanism of action. However, exactly how it causes death of motor neurons, and how its actionsmay interact with other neurotoxins or pathological conditions, is not well understood. The focus of study on the mecha-nism of BMAA toxicity has been on its action as a glutamate receptor agonist. There is evidence that BMAA has effectson all of the main types of glutamate receptors: NMDA, AMPA/kainate, and metabotropic receptors. However, recentresults suggest that BMAA may also act through other mechanisms to induce neuronal death. One such action is on thecystine/glutamate antiporter (system xc~-). Through its effect of system xc~-, BMAA can induce oxidative stress and increaseextracellular glutamate. This action of BMAA provides an attractive mechanism for the multiple neurological deficits thatBMAA has been implicated in inducing.