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Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops

机译：统一自闭症谱系观点：对自动调节反馈回路的考虑

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Understanding the mechanisms underlying autism spectrum disorders (ASDs) is a challenging goal. Here we review recent progress on several fronts, including genetics, proteomics, biochemistry, and electrophysiology, that raise motivation for forming a viable pathophysiological hypothesis. In place of a traditionally unidirectional progression, we put forward a framework that extends homeostatic hypotheses by explicitly emphasizing autoregulatory feedback loops and known synaptic biology. The regulated biological feature can be neuronal electrical activity, the collective strength of synapses onto a dendritic branch, the local concentration of a signaling molecule, or the relative strengths of synaptic excitation and inhibition. The sensor of the biological variable (which we have termed the homeostat) engages mechanisms that operate as negative feedback elements to keep the biological variable tightly confined. We categorize known ASD-associated gene products according to their roles in such feedback loops and provide detailed commentary for exemplar genes within each module.
机译：了解自闭症谱系障碍（ASD）的潜在机制是一个具有挑战性的目标。在这里，我们回顾了在遗传学，蛋白质组学，生物化学和电生理学等几个方面的最新进展，这些进展为形成可行的病理生理学假设提供了动力。代替传统的单向进程，我们提出了一个框架，该框架通过明确强调自动调节反馈回路和已知的突触生物学来扩展稳态假设。调节的生物学特征可以是神经元电活动，突触到树突分支上的集体强度，信号分子的局部浓度或突触激发和抑制的相对强度。生物变量的传感器（我们称其为稳态调节器）与用作负反馈元件的机制保持紧密联系。我们根据已知的ASD相关基因产物在此类反馈回路中的作用对其进行分类，并为每个模块内的示例性基因提供详细的注释。

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