Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain.
Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain.
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DOI：
10.1098/rspb.2015.2397
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发表时间：
2016-01-27
期刊：
影响因子：
--
通讯作者：
Banack SA
中科院分区：
文献类型：
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作者：
Cox PA;Davis DA;Mash DC;Metcalf JS;Banack SA
神经纤维缠结（NFT）和β-淀粉样蛋白斑块是阿尔茨海默病和太平洋关岛查莫罗村民所患的一种不寻常的麻痹性疾病的神经学标志。许多患有这种疾病的查莫罗人患有痴呆症，在一些村庄，四分之一的成年人死于这种疾病。像阿尔茨海默氏症一样，关岛肌萎缩侧索硬化症/帕金森痴呆综合症（ALS/PDC）的病因知之甚少。在重复实验中，我们发现，长期饮食暴露于传统查莫罗饮食中存在的蓝藻毒素β-N-甲基氨基-l-丙氨酸（BMAA），触发了NFT和β-淀粉样蛋白沉积物的形成，其结构和密度与死于ALS/PDC的查莫罗人脑组织中发现的相似。用BMAA给药的水果喂养140天的沙蚕（Chlorocebus sabaeus）在大脑中产生了NFT和稀疏的β-淀粉样蛋白沉积。共同管理的膳食氨基酸l-丝氨酸与l-BMAA显着降低密度的NFT。这些发现表明，虽然长期暴露于环境毒素BMAA会引发脆弱个体的神经退行性变，但增加饮食中l-丝氨酸的含量可以降低风险。
Neurofibrillary tangles (NFT) and β-amyloid plaques are the neurological hallmarks of both Alzheimer's disease and an unusual paralytic illness suffered by Chamorro villagers on the Pacific island of Guam. Many Chamorros with the disease suffer dementia, and in some villages one-quarter of the adults perished from the disease. Like Alzheimer's, the causal factors of Guamanian amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) are poorly understood. In replicated experiments, we found that chronic dietary exposure to a cyanobacterial toxin present in the traditional Chamorro diet, β-N-methylamino-l-alanine (BMAA), triggers the formation of both NFT and β-amyloid deposits similar in structure and density to those found in brain tissues of Chamorros who died with ALS/PDC. Vervets (Chlorocebus sabaeus) fed for 140 days with BMAA-dosed fruit developed NFT and sparse β-amyloid deposits in the brain. Co-administration of the dietary amino acid l-serine with l-BMAA significantly reduced the density of NFT. These findings indicate that while chronic exposure to the environmental toxin BMAA can trigger neurodegeneration in vulnerable individuals, increasing the amount of l-serine in the diet can reduce the risk.