Ly P T T, Singh S, Shaw C A
Department of Ophthalmology, The University of British Columbia, Vancouver, British Columbia, Canada.
J Neurosci Res. 2007 Feb 1;85(2):231-7. doi: 10.1002/jnr.21147.
Amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC) is a unique neurodegenerative disease found on the island of Guam. This disease presents as a spectrum of neurological disorders characterized by features of ALS, parkinsonism, dementia, or a combination. The strongest epidemiological link has been to the consumption of the seeds from the cycad plant that purportedly contained a neurotoxin. Mice fed washed cycad flour show signs that mimic ALS-PDC, which include progressive deficits in motor, cognitive, and olfactory functions associated with neuron loss in the spinal cord, nigrostriatal system, cortex, hippocampus, and olfactory bulb. Through a series of chemical extractions of washed cycad flour, we identified steryl glycoside molecules as bioactive molecules that are neurotoxic in culture and in mice. A detailed review of this class of molecule revealed that the molecules are abundant in the environment, particularly in plants and bacteria. Lipid analysis showed that some bacteria that are associated with some forms of neurodegenerative disorders have the capacity to synthesize steryl glycosides. Furthermore, certain steryl glycosides have been found to be a cell stress mediator and may have some immunomodulary effects. We hypothesize that steryl glycosides are putative neurotoxins involved in the etiopathogenesis of several age-related neurodegenerative disorders.
肌萎缩侧索硬化-帕金森病痴呆综合征（ALS-PDC）是关岛发现的一种独特的神经退行性疾病。这种疾病表现为一系列神经障碍，其特征为肌萎缩侧索硬化、帕金森病、痴呆或这些症状的组合。最有力的流行病学关联是与苏铁植物种子的食用有关，据称这些种子含有一种神经毒素。喂食经过清洗的苏铁面粉的小鼠表现出模仿ALS-PDC的症状，包括运动、认知和嗅觉功能的进行性缺陷，这与脊髓、黑质纹状体系统、皮质、海马体和嗅球中的神经元损失有关。通过对经过清洗的苏铁面粉进行一系列化学提取，我们鉴定出甾体糖苷分子是在培养物和小鼠中具有神经毒性的生物活性分子。对这类分子的详细综述表明，这些分子在环境中大量存在，尤其是在植物和细菌中。脂质分析表明，一些与某些形式的神经退行性疾病相关的细菌具有合成甾体糖苷的能力。此外，某些甾体糖苷已被发现是一种细胞应激介质，可能具有一些免疫调节作用。我们假设甾体糖苷是参与几种与年龄相关的神经退行性疾病发病机制的推定神经毒素。
