Magdalon Juliana, Sánchez-Sánchez Sandra M, Griesi-Oliveira Karina, Sertié Andréa L
Hospital Israelita Albert Einstein, Centro de Pesquisa Experimental, São Paulo 05652-900, Brazil.
Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo 05508-090, Brazil.
Int J Mol Sci. 2017 Mar 18;18(3):659. doi: 10.3390/ijms18030659.
Whereas autism spectrum disorder (ASD) exhibits striking heterogeneity in genetics and clinical presentation, dysfunction of mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway has been identified as a molecular feature common to several well-characterized syndromes with high prevalence of ASD. Additionally, recent findings have also implicated mTORC1 signaling abnormalities in a subset of nonsyndromic ASD, suggesting that defective mTORC1 pathway may be a potential converging mechanism in ASD pathology across different etiologies. However, the mechanistic evidence for a causal link between aberrant mTORC1 pathway activity and ASD neurobehavioral features varies depending on the ASD form involved. In this review, we first discuss six monogenic ASD-related syndromes, including both classical and potentially novel mTORopathies, highlighting their contribution to our understanding of the neurobiological mechanisms underlying ASD, and then we discuss existing evidence suggesting that aberrant mTORC1 signaling may also play a role in nonsyndromic ASD.
鉴于自闭症谱系障碍（ASD）在遗传学和临床表现上具有显著的异质性，雷帕霉素复合物1（mTORC1）信号通路功能障碍已被确定为几种具有高ASD患病率的特征明确的综合征所共有的分子特征。此外，最近的研究结果还表明，mTORC1信号异常存在于一部分非综合征性ASD中，这表明有缺陷的mTORC1通路可能是不同病因的ASD病理中潜在的共同机制。然而，mTORC1通路异常活动与ASD神经行为特征之间因果关系的机制证据因所涉及的ASD类型而异。在这篇综述中，我们首先讨论六种与单基因ASD相关的综合征，包括经典的和潜在的新型mTOR病，强调它们对我们理解ASD潜在神经生物学机制的贡献，然后我们讨论现有证据表明异常的mTORC1信号可能在非综合征性ASD中也起作用。
