Qiu Zilong, Cheng Ju
Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Neurosignals. 2010;18(2):72-81. doi: 10.1159/000320970. Epub 2010 Oct 19.
During the last decade, autism spectrum disorders (ASD) have become the center of attention where several branches of modern biology unexpectedly meet, such as neural development, molecular biology, epigenetics, neurophysiology and psychiatry. This review will focus on the molecular mechanism by which calcium-dependent gene expression regulates brain development and how ASD may occur if this process is compromised. Specifically, the studies of the calcium-dependent transcriptional repressor MeCP2 gave us much insight about how abnormal development may lead to ASD. Most recently, studies about Ube3a, a critical component of the ubiquitination system enzyme, shed light on how neural activity regulates synapse function through the protein degradation pathway. Taken together, these studies suggest that ASD may be caused by the incapability of neurons to generate adaptive responses via regulating gene expression upon incoming activity.
在过去十年中，自闭症谱系障碍（ASD）已成为现代生物学多个分支意外交汇的焦点，这些分支包括神经发育、分子生物学、表观遗传学、神经生理学和精神病学。本综述将聚焦于钙依赖性基因表达调节大脑发育的分子机制，以及如果这一过程受损可能如何引发ASD。具体而言，对钙依赖性转录抑制因子MeCP2的研究让我们深入了解了异常发育如何导致ASD。最近，关于泛素化系统酶的关键成分Ube3a的研究揭示了神经活动如何通过蛋白质降解途径调节突触功能。综上所述，这些研究表明，ASD可能是由于神经元在接收到传入活动时无法通过调节基因表达产生适应性反应所致。
