孤独症谱系障碍的遗传病因和神经生物学机制  

Genetic etiology and neurobiological mechanisms of autism spectrum disorders

作　　者：张竞 贾相斌 夏昆[1,2,3,4,5] 郭辉[1,2,4,5] 李家大[1,2,4,5] ZHANG Jing;JIA XiangBin;XIA Kun;GUO Hui;LI JiaDa(Center for Medical Genetics,Central South University,Changsha 410078,China;School of Life Sciences,Central South University,Changsha 410013,China;MOE Key Lab of Rare Pediatric Diseases,Central South University,Changsha 410199,China;Hunan Key Laboratory of Animal Models for Human Diseases,Central South University,Changsha 410078,China;Hunan Key Laboratory of Medical Genetics,Central South University,Changsha 410078,China)

机构地区：[1]中南大学医学遗传学研究中心,长沙410078 [2]中南大学生命科学学院,长沙410013 [3]中南大学儿科罕见病教育部重点实验室,长沙410199 [4]中南大学人类重大疾病动物模型研究湖南省重点实验室,长沙410078 [5]中南大学医学遗传学湖南省重点实验室,长沙410078

出　　处：《中国科学：生命科学》2024年第11期2051-2067,共17页Scientia Sinica(Vitae)

基　　金：国家自然科学基金(批准号:32371218);湖南省自然科学基金(批准号:2024JJ6552,2024JJ6545);中国博士后科学基金(批准号:2023M733969)资助。

摘　　要：孤独症谱系障碍是一种常见的严重影响儿童健康的神经发育障碍疾病,主要表现为社交障碍及重复刻板行为,尚无有效治疗手段,给社会和家庭带来沉重负担.因此,研究孤独症病因学、探索防治新方法具有重要理论和实践意义.孤独症病因复杂,遗传和环境因素均参与其中.对孤独症风险基因功能的系统研究,发现了潜在的神经生物学病理机制和共同信号通路.基因-环境交互作用在孤独症病因学中的重要作用也被逐步揭示,将为孤独症研究提供一个全新切入点.此外,动物模型的运用推动了孤独症病因学研究、药物开发等领域迅速发展,开发新的动物模型十分必要.对孤独症发病机制的深入认识将促进生物标记物或治疗靶点的发现,为孤独症“早诊断、早预警、早干预”提供理论基础和必要支持.Autism spectrum disorder is a common neurodevelopmental disorder that seriously affects children’s health,characterized by deficits in social interactions and repetitive behavior/restricted interests.There is no effective treatment,which brings heavy burden to society and families.Therefore,it is of great theoretical and practical significance to study the etiology of autism and explore new ways to prevent and cure autism.The causes of autism are complex,and both genetic and environmental factors are involved.Systematic studies on the function of autism risk genes have revealed the underlying neurobiological pathologic mechanisms and involved common signaling pathways of autism.More and more evidence shows that gene-environment interaction plays an important role in the etiology of autism,which will provide a possible new entry point for autism research.In addition,the application of animal models has promoted the rapid development of autism etiology research,and drug development,so it is necessary to develop new animal models.In-depth understanding of the pathogenesis of autism will promote the discovery of biomarkers or therapeutic targets,and provide theoretical basis and necessary support for the“early diagnosis,early warning and early intervention”of autism.

关 键 词：孤独症谱系障碍 遗传病因 神经环路 分子通路 动物模型 

分 类 号：R749.94[医药卫生—神经病学与精神病学]