Ammonium chloride and tunicamycin are novel toxins for dopaminergic neurons and induce Parkinson's disease-like phenotypes in medaka fish
Ammonium chloride and tunicamycin are novel toxins for dopaminergic neurons and induce Parkinson's disease-like phenotypes in medaka fish
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DOI：
10.1111/j.1471-4159.2010.07012.x
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发表时间：
2010-12-01
影响因子：
4.7
通讯作者：
Takahashi, Ryosuke
中科院分区：
文献类型：
--
作者：
Matsui, Hideaki;Ito, Hidefumi;Takahashi, Ryosuke
蛋白质折叠和降解的紊乱是包括帕金森病(PD)在内的神经退行性疾病的关键病理机制。最近的证据表明，蛋白质的错误处理可能在帕金森病的发病机制中发挥重要作用。我们已经利用青竹鱼来监测向脑脊液空间注射神经毒素的效果。在这项研究中，测试了氯化铵、衣霉素和lactacystin分别对溶酶体蛋白分解、内质网N-糖基化和蛋白酶体降解的影响。所有被测试的物质都会导致多巴胺能神经元的选择性丧失、运动障碍和包涵体。其中，氯化铵注射后形成的包涵体的特征与PD相似：泛素和磷酸化的α-突触核蛋白共存，包涵体中存在LC3蛋白。我们的研究表明，青冈鱼有助于检测环境毒素和溶酶体抑制的影响，而溶酶体抑制物可能是发育过程中的因素。
Perturbations in protein folding and degradation are key pathological mechanisms in neurodegenerative diseases, including Parkinson's disease (PD). Recent evidence suggests that mishandling of proteins may play an important role in the pathogenesis of PD. We have utilized medaka fish to monitor the effects of injecting neurotoxins into the CSF space. In this study, ammonium chloride, tunicamycin, and lactacystin were tested for their ability to disturb lysosomal proteolysis, N-glycosylation in the endoplasmic reticulum, and proteasomal degradation, respectively. All of the substances tested induced selective loss of dopaminergic neurons, movement disorders and inclusion bodies. Among them, the features of the inclusion bodies that developed after ammonium chloride injection mimicked those of PD: co-localization of ubiquitin and phosphorylated alpha-synuclein, as well as the presence of LC3 protein in the inclusion bodies. Our study demonstrated that medaka fish are useful for examining the effects of environmental toxins and lysosome inhibition, and lysosome inhibitors may be factors in the development