Oxidative stress in autism.
Oxidative stress in autism.
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DOI：
10.1016/j.pathophys.2006.05.007
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发表时间：
2006-08-01
期刊：
影响因子：
--
通讯作者：
Chauhan, Ved
中科院分区：
文献类型：
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作者：
Chauhan, Abha;Chauhan, Ved
自闭症是一种严重的发育障碍，病因学知之甚少。自闭症中的氧化应激已经在膜水平上进行了研究，也通过测量脂质过氧化产物，解毒剂（如谷胱甘肽）和抗氧化剂参与防御系统对抗活性氧（ROS）。脂质过氧化标记物在自闭症中升高，表明这种疾病的氧化应激增加。自闭症儿童的主要抗氧化血清蛋白，即转铁蛋白（铁结合蛋白）和铜蓝蛋白（铜结合蛋白）的水平降低。这些蛋白质水平的降低与自闭症儿童先前获得的语言技能的丧失之间存在正相关。铜蓝蛋白和转铁蛋白水平的改变可能导致自闭症患者铁和铜代谢异常。膜磷脂，活性氧的主要目标，也改变了自闭症。与未受影响的兄弟姐妹相比，自闭症儿童红细胞膜中的磷脂酰乙醇胺（PE）水平降低，磷脂酰丝氨酸（PS）水平升高。一些研究表明，自闭症患者体内的抗氧化酶，如超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶的活性发生了变化。此外，谷胱甘肽水平和同型半胱氨酸/甲硫氨酸代谢的改变，炎症增加，兴奋性毒性，以及线粒体和免疫功能障碍已被建议在自闭症。此外，环境和遗传因素可能会增加自闭症患者对氧化应激的脆弱性。总之，这些研究表明自闭症的氧化应激增加可能有助于这种疾病的发展。氧化应激与膜脂异常、炎症反应、异常免疫反应、能量代谢受损和兴奋性毒性有关，导致自闭症的临床症状和发病机制。
Autism is a severe developmental disorder with poorly understood etiology. Oxidative stress in autism has been studied at the membrane level and also by measuring products of lipid peroxidation, detoxifying agents (such as glutathione), and antioxidants involved in the defense system against reactive oxygen species (ROS). Lipid peroxidation markers are elevated in autism, indicating that oxidative stress is increased in this disease. Levels of major antioxidant serum proteins, namely transferrin (iron-binding protein) and ceruloplasmin (copper-binding protein), are decreased in children with autism. There is a positive correlation between reduced levels of these proteins and loss of previously acquired language skills in children with autism. The alterations in ceruloplasmin and transferrin levels may lead to abnormal iron and copper metabolism in autism. The membrane phospholipids, the prime target of ROS, are also altered in autism. The levels of phosphatidylethanolamine (PE) are decreased, and phosphatidylserine (PS) levels are increased in the erythrocyte membrane of children with autism as compared to their unaffected siblings. Several studies have suggested alterations in the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase in autism. Additionally, altered glutathione levels and homocysteine/methionine metabolism, increased inflammation, excitotoxicity, as well as mitochondrial and immune dysfunction have been suggested in autism. Furthermore, environmental and genetic factors may increase vulnerability to oxidative stress in autism. Taken together, these studies suggest increased oxidative stress in autism that may contribute to the development of this disease. A mechanism linking oxidative stress with membrane lipid abnormalities, inflammation, aberrant immune response, impaired energy metabolism and excitotoxicity, leading to clinical symptoms and pathogenesis of autism is proposed.