β-N-甲基氨基-L-丙氨酸通过多种机制增强神经毒性。
Beta-N-methylamino-L-alanine enhances neurotoxicity through multiple mechanisms.
作者信息
Lobner Doug, Piana Peachy Mae T, Salous Abed K, Peoples Robert W
机构信息
Department of Biomedical Sciences, Marquette University, 561 N. 15th Street, Rm 426, Milwaukee, WI 53233, USA.
出版信息
Neurobiol Dis. 2007 Feb;25(2):360-6. doi: 10.1016/j.nbd.2006.10.002. Epub 2006 Nov 13.
Abstract
The idea that the environmental toxin beta-N-methylamino-l-alanine (BMAA) is involved in neurodegenerative diseases on Guam has risen and fallen over the years. The theory has gained greater interest with recent reports that BMAA is biomagnified, is widely distributed around the planet, and is present in the brains of Alzheimer's patients in Canada. We provide two important new findings. First, we show that BMAA at concentrations as low as 10 muM can potentiate neuronal injury induced by other insults. This is the first evidence that BMAA at concentrations below the mM range can enhance death of cortical neurons and illustrates potential synergistic effects of environmental toxins with underlying neurological conditions. Second, we show that the mechanism of BMAA toxicity is threefold: it is an agonist for NMDA and mGluR5 receptors, and induces oxidative stress. The results provide further support for the hypothesis that BMAA plays a role in neurodegenerative diseases.
摘要
多年来，关于环境毒素β-N-甲基氨基-L-丙氨酸（BMAA）与关岛神经退行性疾病有关的观点起起伏伏。随着近期有报道称BMAA会生物放大、在全球广泛分布且存在于加拿大阿尔茨海默病患者的大脑中，该理论引发了更大关注。我们有两项重要的新发现。其一，我们发现低至10微摩尔浓度的BMAA就能增强由其他损伤诱导的神经元损伤。这是首次有证据表明低于毫摩尔范围浓度的BMAA能增强皮质神经元死亡，并说明了环境毒素与潜在神经疾病之间可能存在的协同效应。其二，我们发现BMAA毒性机制有三方面：它是NMDA和mGluR5受体的激动剂，并能诱导氧化应激。这些结果为BMAA在神经退行性疾病中起作用这一假说提供了进一步支持。
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