Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio-Medico, Rome, Italy.
Neurobiol Dis. 2012 Jan;45(1):57-68. doi: 10.1016/j.nbd.2010.11.010. Epub 2010 Dec 2.
Though different in their aetiology, autism spectrum disorder (ASD), Rett syndrome (RTT) and Down syndrome (DS) are three neurodevelopmental disorders sharing significant clinical and neuropathological overlaps. Genome-wide expression studies are reviewed and available datasets from post-mortem brains reanalyzed to identify genes and gene pathways dysregulated in all three disorders. Our results surprisingly converge upon immune, and not neurodevelopmental genes, as the most consistently shared abnormality in genome-wide expression patterns. A dysregulated immune response, accompanied by enhanced oxidative stress and abnormal mitochondrial metabolism seemingly represents the common molecular underpinning of these neurodevelopmental disorders. This conclusion may be important for the definition of pharmacological therapies able to ameliorate clinical symptoms across these disorders.
虽然自闭症谱系障碍(ASD)、雷特综合征(RTT)和唐氏综合征(DS)在病因上有所不同,但它们是三种具有显著临床和神经病理学重叠的神经发育障碍。本文回顾了全基因组表达研究,并重新分析了来自尸检大脑的现有数据集,以确定这三种疾病中失调的基因和基因途径。我们的结果令人惊讶地集中在免疫基因上,而不是神经发育基因上,因为这些基因在全基因组表达模式中是最一致的异常。失调的免疫反应伴随着增强的氧化应激和异常的线粒体代谢,似乎代表了这些神经发育障碍的共同分子基础。这一结论对于定义能够改善这些疾病临床症状的药物治疗方法可能很重要。