Center of Oxidative Stress Research, Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Neuromolecular Med. 2013 Jun;15(2):364-83. doi: 10.1007/s12017-013-8224-3. Epub 2013 Mar 2.
Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication accompanied with repetitive behavioral patterns and unusual stereotyped interests. Autism is considered a highly heterogeneous disorder with diverse putative causes and associated factors giving rise to variable ranges of symptomatology. Incidence seems to be increasing with time, while the underlying pathophysiological mechanisms remain virtually uncharacterized (or unknown). By systematic review of the literature and a systems biology approach, our aims were to examine the multifactorial nature of autism with its broad range of severity, to ascertain the predominant biological processes, cellular components, and molecular functions integral to the disorder, and finally, to elucidate the most central contributions (genetic and/or environmental) in silico. With this goal, we developed an integrative network model for gene-environment interactions (GENVI model) where calcium (Ca(2+)) was shown to be its most relevant node. Moreover, considering the present data from our systems biology approach together with the results from the differential gene expression analysis of cerebellar samples from autistic patients, we believe that RAC1, in particular, and the RHO family of GTPases, in general, could play a critical role in the neuropathological events associated with autism.
自闭症是一种神经发育障碍，其特征是社交互动和沟通受损，同时伴有重复的行为模式和异常的刻板兴趣。自闭症被认为是一种高度异质的疾病，具有多种潜在的病因和相关因素，导致症状的范围各不相同。发病率似乎随着时间的推移而增加，而潜在的病理生理机制实际上尚未得到描述（或未知）。通过对文献的系统回顾和系统生物学方法，我们的目的是检查自闭症的多因素性质及其广泛的严重程度，确定与该疾病相关的主要生物学过程、细胞成分和分子功能，并最终从理论上阐明最主要的贡献（遗传和/或环境）。为此，我们开发了一个用于基因-环境相互作用（GENVI 模型）的综合网络模型，其中钙（Ca(2+))被证明是其最相关的节点。此外，考虑到我们从系统生物学方法获得的当前数据以及自闭症患者小脑样本的差异基因表达分析结果，我们认为 RAC1 特别是 RHO 家族的 GTPases 可能在与自闭症相关的神经病理事件中发挥关键作用。
