Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Int J Mol Sci. 2021 Mar 10;22(6):2811. doi: 10.3390/ijms22062811.
Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition associated with impairments in social interaction, communication and repetitive behaviors. While the underlying disease mechanisms remain to be fully elucidated, dysfunction of neuronal plasticity and local translation control have emerged as key points of interest. Translation of mRNAs for critical synaptic proteins are negatively regulated by Fragile X mental retardation protein (FMRP), which is lost in the most common single-gene disorder associated with ASD. Numerous studies have shown that mRNA transport, RNA metabolism, and translation of synaptic proteins are important for neuronal health, synaptic plasticity, and learning and memory. Accordingly, dysfunction of these mechanisms may contribute to the abnormal brain function observed in individuals with autism spectrum disorder (ASD). In this review, we summarize recent studies about local translation and mRNA processing of synaptic proteins and discuss how perturbations of these processes may be related to the pathophysiology of ASD.
自闭症谱系障碍（ASD）是一种遗传性神经发育障碍，与社交互动、沟通和重复行为障碍有关。尽管潜在的疾病机制仍未完全阐明，但神经元可塑性和局部翻译控制的功能障碍已成为关注的焦点。关键突触蛋白的 mRNA 翻译受到脆性 X 智力迟钝蛋白 (FMRP) 的负调控，而 FMRP 在与 ASD 相关的最常见的单基因疾病中缺失。许多研究表明，mRNA 运输、RNA 代谢和突触蛋白的翻译对于神经元健康、突触可塑性以及学习和记忆至关重要。因此，这些机制的功能障碍可能导致自闭症谱系障碍（ASD）患者大脑功能异常。在这篇综述中，我们总结了最近关于突触蛋白的局部翻译和 mRNA 加工的研究，并讨论了这些过程的扰动如何与 ASD 的病理生理学相关。
