Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, 21 Sassoon Road, Hong Kong, China.
State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, 21 Sassoon Road, Hong Kong, China.
Dev Neurobiol. 2019 Jan;79(1):20-35. doi: 10.1002/dneu.22644. Epub 2018 Oct 21.
Synapses are the basic structural and functional units for information processing and storage in the brain. Their diverse properties and functions ultimately underlie the complexity of human behavior. Proper development and maintenance of synapses are essential for normal functioning of the nervous system. Disruption in synaptogenesis and the consequent alteration in synaptic function have been strongly implicated to cause neurodevelopmental disorders such as autism spectrum disorders (ASDs) and schizophrenia (SCZ). The introduction of human-induced pluripotent stem cells (hiPSCs) provides a new path to elucidate disease mechanisms and potential therapies. In this review, we will discuss the advantages and limitations of using hiPSC-derived neurons to study synaptic disorders. Many mutations in genes encoding for proteins that regulate synaptogenesis have been identified in patients with ASDs and SCZ. We use Methyl-CpG binding protein 2 (MECP2), SH3 and multiple ankyrin repeat domains 3 (SHANK3) and Disrupted in schizophrenia 1 (DISC1) as examples to illustrate the promise of using hiPSCs as cellular models to elucidate the mechanisms underlying disease-related synaptopathy.
突触是大脑中信息处理和存储的基本结构和功能单位。它们多样的性质和功能最终构成了人类行为的复杂性。突触的正常发育和维持对于神经系统的正常功能至关重要。突触发生的破坏以及随之而来的突触功能改变，与自闭症谱系障碍（ASD）和精神分裂症（SCZ）等神经发育障碍密切相关。人诱导多能干细胞（hiPSC）的引入为阐明疾病机制和潜在治疗方法提供了新途径。在这篇综述中，我们将讨论使用 hiPSC 衍生神经元研究突触障碍的优缺点。在 ASD 和 SCZ 患者中，已经鉴定出许多编码调节突触发生的蛋白质的基因突变。我们以甲基化 CpG 结合蛋白 2（MECP2）、SH3 和多个锚蛋白重复域 3（SHANK3）和精神分裂症 1 区（DISC1）为例，说明了使用 hiPSC 作为细胞模型来阐明与疾病相关的突触病变的机制的前景。
