Dept. of Biomedical Sciences, Marquette University, 561 N. 15th Street, Rm 426,Milwaukee, WI, 53233, USA.
Dept. of Biomedical Sciences, Marquette University, 561 N. 15th Street, Rm 426,Milwaukee, WI, 53233, USA.
Toxicon. 2020 Sep;184:175-179. doi: 10.1016/j.toxicon.2020.06.014. Epub 2020 Jun 23.
There is evidence that the environmental toxin β-N-methylamino-L-alanine (L-BMAA) may be involved in neurodegenerative diseases. However, a number of controversies exist regarding L-BMAA, one of which is the possibility that when assaying for L-BMAA, its isomers are being detected instead. There are at least four isomers of BMAA that are known to occur: L-BMAA, β-N-methylamino-D-alanine (D-BMAA), 2,4-diaminobutyric acid (DAB), and N-(2-aminoethyl)glycine (AEG). The fact that isomers of BMAA exist in nature also leads to the possibility that they are involved in toxicity. We set out to determine both the potency and the mechanism of toxicity of L-BMAA, D-BMAA, DAB, asnd AEG using primary cortical cultures. The results were surprising with the following order of potency of toxicity: AEG > DAB > D-BMAA > L-BMAA. These results suggest that AEG may be an overlooked neurotoxin. We found that AEG induced toxicity through mGluR5 receptors and induction of oxidative stress. While the potential role of L-BMAA in neurodegenerative diseases has been emphasized, other isomers of L-BMAA, particularly AEG, are actually more potent toxins, and could therefore potentially contribute to neurodegenerative diseases.
有证据表明，环境毒素β-N-甲基氨基-L-丙氨酸（L-BMAA）可能与神经退行性疾病有关。然而，关于 L-BMAA 存在许多争议，其中之一是在检测 L-BMAA 时，可能会检测到其异构体。已知 BMAA 至少有四种异构体：L-BMAA、β-N-甲基氨基-D-丙氨酸（D-BMAA）、2,4-二氨基丁酸（DAB）和 N-（2-氨基乙基）甘氨酸（AEG）。BMAA 异构体存在于自然界中，这也使得它们可能参与毒性作用成为可能。我们着手使用原代皮质培养物来确定 L-BMAA、D-BMAA、DAB 和 AEG 的毒性效力和机制。结果令人惊讶，毒性效力的顺序如下：AEG>DAB>D-BMAA>L-BMAA。这些结果表明 AEG 可能是一种被忽视的神经毒素。我们发现 AEG 通过 mGluR5 受体诱导毒性，并诱导氧化应激。虽然 L-BMAA 在神经退行性疾病中的潜在作用已得到强调，但 L-BMAA 的其他异构体，特别是 AEG，实际上是更有效的毒素，因此可能有助于神经退行性疾病。
