Abdulla E M, Campbell I C
Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
Ann N Y Acad Sci. 1993 May 28;679:276-9. doi: 10.1111/j.1749-6632.1993.tb18308.x.
This work shows that the neurotoxic excitatory amino acids beta-N-methylamino alanine, BMAA, and kainate, modulate neurite outgrowth; this was assessed by measuring the levels of two separate neurofilament proteins (68 kD and 160 kD), in a mouse neuroblastoma cell line, (NB41A3). BMAA has been proposed to be the exogenous excitotoxin in Guam disease or amyotrophic lateral sclerosis (ALS/parkinsonian/dementia; Guam ALS-PD). Kainate is a glutamate analogue which causes excitotoxic damage associated with excessive entry of calcium into neurons. The results show that at low doses (10(-9) to 10(-7) M) both BMAA and kainate decrease the concentration of the two neurofilament proteins. However at high doses (10(-6) to 10(-5) M) they cause an apparent accumulation of the neurofilament proteins; the effect is more marked with BMAA. These results support the continued development of an in vitro test for neurotoxicity based on neurite outgrowth.
这项研究表明，神经毒性兴奋性氨基酸β-N-甲基氨基-L-丙氨酸（BMAA）和红藻氨酸可调节神经突生长；这是通过测量小鼠神经母细胞瘤细胞系（NB41A3）中两种不同神经丝蛋白（68 kD和160 kD）的水平来评估的。BMAA被认为是关岛病或肌萎缩侧索硬化症（ALS/帕金森病/痴呆症；关岛ALS-PD）中的外源性兴奋毒素。红藻氨酸是一种谷氨酸类似物，可导致与钙离子过度进入神经元相关的兴奋毒性损伤。结果表明，在低剂量（10^(-9)至10^(-7) M）时，BMAA和红藻氨酸都会降低两种神经丝蛋白的浓度。然而，在高剂量（10^(-6)至10^(-5) M）时，它们会导致神经丝蛋白明显积累；BMAA的这种作用更为显著。这些结果支持基于神经突生长继续开发神经毒性体外试验。
