基于突触功能异常的自闭症发病机制研究进展

Advances in the Understanding of the Pathology of Autism Focusing on Synapse Dysfunction

关键词:  自闭症  发病机制  突触功能异常  基因突变  信号通路

Key words:  autism  pathogenesis  synaptic function disorders  genic mutation  signaling pathway

摘要:

作为神经元间行使功能和信息传递的关键部位，突触的功能异常在自闭症病理过程中扮演的角色备受关注。在自闭症动物模型或患者中，突触形态学发生了变化，主要表现为树突棘密度、树突棘形态比例及突触后致密物质的异常，这些可能与突触的发生、修剪及成熟过程受到干扰相关。此外，相关突触蛋白如NLGNs、NRXNs和SHANK3等在自闭症患者中均发生了突变。实验研究也发现多条信号通路通过改变突触功能从而影响了自闭症疾病模型的社会交往能力。截止目前为止，自闭症的病理机制和药物靶标仍未可知。本文就基于突触功能异常的自闭症发病机制研究进行综述。

Abstract:

Synapse is an essential component in function and information transmission between neurons, hence the role its dysfunction played in the pathology of autism has received much attention. The synaptic morphology changes have been found in animal model or patients of autism, mainly manifested by abnormalities in dendritic spine density, proportion of the dendritic spines and postsynaptic density(PSD), which are possibly correlated with interruptions in formation, maturation and maintenance of synapses. In addition, deletions and point mutations of the synaptic proteins such as NRXNs, SHANK3, NLGNs genes have been detected in ASD individuals. Multiple signaling pathways have been reported to affect the social contact ability in ASD models, possibly caused by synapse function disruptions. Until now, the pathogenesis and drug targets of autism still remains unknown, and thus pose great challenges to further studies. This review focuses on the role of synaptic dysfunction in human ASD.