A Subset of Autism-Associated Genes Regulate the Structural Stability of Neurons.
A Subset of Autism-Associated Genes Regulate the Structural Stability of Neurons.
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DOI：
10.3389/fncel.2016.00263
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发表时间：
2016
影响因子：
5.3
通讯作者：
Blatt GJ
中科院分区：
文献类型：
--
作者：
Lin YC;Frei JA;Kilander MB;Shen W;Blatt GJ
自闭症谱系障碍 (ASD) 包括一系列影响个人与他人沟通和互动能力的神经系统疾病。自闭症谱系障碍患者经常在社交互动、沟通和行为方面表现出明显的质量困难。神经突树枝化和树突棘形态的改变，包括大小、形状和数量，是几乎所有神经系统疾病（包括自闭症谱系障碍）的标志。随着近年来实验证据的出现，越来越明显的是，尽管已识别的自闭症风险基因存在广泛的异质性，但其中许多基因汇聚成相似的细胞途径，包括调节神经突生长、突触形成和脊柱稳定性以及突触可塑性的途径。这些机制共同调节神经元的结构稳定性，并且是自闭症谱系障碍中的脆弱目标。在这篇综述中，我们讨论了目前对影响神经元结构连接的自闭症风险基因的理解。我们将它们细分为（1）细胞骨架调节剂，例如马达和小型 RhoGTPase 调节剂； (2)粘附分子，例如钙粘蛋白、NCAM和神经毒素超家族； (3)细胞表面受体，例如谷氨酸受体、酪氨酸激酶受体； (4)信号分子，例如蛋白激酶和磷酸酶； (5)突触蛋白，例如囊泡和支架蛋白。尽管其中一些基因在维持神经元结构稳定性中的作用已得到充分研究，但突变如何导致自闭症表型仍然很大程度上未知。研究这些基因突变时神经元结构和功能是否以及如何受到影响将为开发旨在改善自闭症患者及其家人的生活的有效干预措施提供见解。
Autism spectrum disorder (ASD) comprises a range of neurological conditions that affect individuals’ ability to communicate and interact with others. People with ASD often exhibit marked qualitative difficulties in social interaction, communication, and behavior. Alterations in neurite arborization and dendritic spine morphology, including size, shape, and number, are hallmarks of almost all neurological conditions, including ASD. As experimental evidence emerges in recent years, it becomes clear that although there is broad heterogeneity of identified autism risk genes, many of them converge into similar cellular pathways, including those regulating neurite outgrowth, synapse formation and spine stability, and synaptic plasticity. These mechanisms together regulate the structural stability of neurons and are vulnerable targets in ASD. In this review, we discuss the current understanding of those autism risk genes that affect the structural connectivity of neurons. We sub-categorize them into (1) cytoskeletal regulators, e.g., motors and small RhoGTPase regulators; (2) adhesion molecules, e.g., cadherins, NCAM, and neurexin superfamily; (3) cell surface receptors, e.g., glutamatergic receptors and receptor tyrosine kinases; (4) signaling molecules, e.g., protein kinases and phosphatases; and (5) synaptic proteins, e.g., vesicle and scaffolding proteins. Although the roles of some of these genes in maintaining neuronal structural stability are well studied, how mutations contribute to the autism phenotype is still largely unknown. Investigating whether and how the neuronal structure and function are affected when these genes are mutated will provide insights toward developing effective interventions aimed at improving the lives of people with autism and their families.
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