PLANT TOXINS AND DEMENTIA

植物毒素与痴呆症

• 批准号: 2051857
• 负责人: TOM J MABRY
• 金额: $ 9.15万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2051857
• 关键词: Pacific Islands; alanine; aminoacid analog; aminoacid analyzer; gas chromatography; glutamates; high voltage electrophoresis; mass spectrometry; neurotoxins; nutrition related tag; pathogenic diet; plant extracts; plant poisoning; tissue /cell culture

Lathyrism, a motorneurone disease of India and Africa, is caused by beta-oxalylaminoalanine (L-BOAA) which is present in the seeds of the legume Lathyrus sativus. The seeds of this plant are ground to a flour and used as food. Circumstantial evidence suggests that a second neurotoxic non-protein amino acid, beta-methylaminoalanine (L-BMAA), which is present in seeds of Cycas circinalis, which is used as a source of starchy foods by the Chamorro people of Guam and elsewhere in the western Pacific, may be responsible for amyotrophic lateral sclerosis- Parkinsonism dementia (ALS-PDC) among these people. Both of these non- protein amino acids induce motor system disorders when fed to macaques and both are glutamate agonists. Another glutamate agonist domoic acid, which was implicated in Canada in a 1987 outbreak of neurologic disorders by persons who had eaten contaminated mussels, also has similar ionic functions in almost the same stereochemical orientation as do glutamic acid, NMDA, kainic acid, L-BOAA and, significantly, the physiological-stable complex of L-BMAA with carbonate, a common physiological ion. In order to provide more comprehensive data on the potential toxicity of Cycas circinalis from Guam it is proposed to determine the concentrations of not only free L-BMAA, but also peptide-bound L-BMAA, L-BMAA precursors and related glutamate analogues in all organs of the plant using material from different plant populations. The structures of any unusual amino acids or related compounds will be determined, and isolated compounds will be evaluated for neurotoxicity. We have already detected several unknown ninhydrin-positive compounds in the extract of Cycas circinalis seeds in addition to the known L-BMAA. It is possible that some forms of Parkinson's and Alzheimer's diseases and ALS found in the continental United States may involve dietary factors. It is therefore also proposed to determine simultaneously whether any of the major crop species that contribute to the American diet contain glutamate agonists or antagonists which, if ingested for a prolonged period, could induce motor systems disorders. Plant extracts will be analyzed with high voltage electrophoresis, an automatic amino acid analyzer and GC/MS. Isolations will be made on ion-exchange columns. Neurotoxicity will first be evaluated in cultured tissues. Compounds will be selected for animal testing on the basis of ionic functions, stereochemistry and glutamate agonist activity.

lathyrism是印度和非洲的一种运动神经元疾病，是由 β-氧素氨基氨基氨酸（L-BOAA），存在于种子中 豆科氏木sativus。 该植物的种子被磨成面粉 并用作食物。 间接证据表明第二个 神经毒性非蛋白氨基酸，β-甲基氨基氨基氨酸（L-BMAA）， 它存在于圆环的种子中，该种子用作源 关岛和其他地方其他地方的淀粉食品 西太平洋，可能是肌萎缩性侧面硬化症的原因 这些人中的帕金森主义痴呆症（ALS-PDC）。 这两个非 - 蛋白质氨基酸诱导运动系统疾病，当 两者都是谷氨酸激动剂。 另一个谷氨酸激动剂domoic酸， 这与1987年的神经系统爆发有关 食用被污染贻贝的人的疾病，也有 在几乎相同的立体化学方向上，相似的离子功能与 做谷氨酸，NMDA，海藻酸，L-BOAA以及明显的 L-BMAA与碳酸盐的生理稳定复合物，一种常见 生理离子。 为了提供有关潜在毒性的更全面的数据 关岛的赛车圆形圆形圆形圆周拟议中提议确定 不仅是游离L-BMAA的浓度，还包括肽结合的L-BMAA， L-BMAA前体和相关的谷氨酸类似物 使用来自不同植物种群的材料的植物。 结构 将确定任何异常氨基酸或相关化合物的 分离的化合物将用于神经毒性。 我们已经 在提取物中检测到了几种未知的二氢蛋白阳性化合物 除了已知的L-BMAA外，Cycas Circinalis种子。 某些形式的帕金森氏症和阿尔茨海默氏症的疾病可能有可能 在美国大陆发现的ALS可能涉及饮食 因素。 因此，还建议同时确定 是否有任何有助于美国的主要农作物物种 饮食中含有谷氨酸激动剂或拮抗剂，如果摄入 延长时期可能会诱发运动系统障碍。 植物提取物将用高压电泳分析 自动氨基酸分析仪和GC/MS。 隔离将进行 离子交换列。 神经毒性将首先在培养中评估 组织。 根据 离子功能，立体化学和谷氨酸激动剂活性。