摘要
神经管畸形(neural tube defects,NTDs)作为一类严重的先天出生缺陷疾病,严重影响着胎儿的生命与健康,其发生机制十分复杂,涉及遗传因素与环境因素之间的复杂作用。近年来,蛋白质组学愈加广泛的应用揭示了组蛋白修饰在表观遗传调控中发挥的关键作用,尤其在NTDs的发病机制中受到广泛关注。组蛋白修饰包括组蛋白甲基化、乙酰化、泛素化、同型半胱氨酸化、丙二酰化和巴豆酰化等多种类型,这些修饰影响神经管闭合关键蛋白的表达对于神经管闭合期间的基因组稳定性至关重要,参与神经管畸形的发生发展,其异常调控与NTDs的发生密切相关。此外,在胚胎大脑发育过程中,这些组蛋白修饰极易受到母体代谢物水平、致畸物质暴露等环境因素的影响。母体代谢物水平的异常会引起关键基因表达调控异常,这些因素影响组蛋白修饰,从而调控下游相关基因的异常表达,包括神经管发育相关基因,导致NTDs等多种神经发育疾病的发生。目前NTDs的机制尽管已有大量研究,但NTDs的确切发病机制仍未完全阐明,深入研究NTDs的致病因素和发生机制对于提高出生人口质量、降低新生儿死亡率具有重要的意义。本文综述了近年关于母体代谢物介导组蛋白修饰异常引起胎儿NTDs发生的研究进展,并对该研究方向进行了展望,以期揭示组蛋白修饰在神经管发育中的关键调控功能,为进一步研究组蛋白修饰与NTDs发生之间的关系提供理论基础,也为NTDs未来的预防和治疗策略提供了理论依据。
Neural tube defects(NTDs)are a category of severe congenital birth defects that seriously affect the life and health of the fetus.The occurrence mechanism is very complex,involving the complex interaction between genetic factors and environmental factors.In recent years,the increasingly widespread application of proteomics has revealed the key role of histone modifications in epigenetic regulation,especially in the pathogenesis of NTDs.Histone modifications include various types such as histone methylation,acetylation,ubiquitination,homocysteinylation,malonylation,and crotonylation.These modifications affect the expression of key proteins involved in neural tube closure and are crucial for genomic stability during neural tube closure,participating in the occurrence and development of NTDs.Abnormal regulation of these regulations is closely related to the occurrence of NTDs.In addition,during embryonic brain development,histone modifications are easily affected by environmental factors such as maternal metabolite levels and exposure to teratogenic substances.Abnormal maternal metabolite levels can cause abnormal regulation of key gene expression,which affects histone modifications and thereby regulates the abnormal expression of downstream related genes,including genes related to neural tube development,leading to the occurrence of NTDs and other neurodevelopmental diseases.Although there have been numerous studies on the mechanism of NTDs,the exact pathogenesis of NTDs has not yet been fully elucidated.In-depth research on the pathogenic factors and occurrence mechanism of NTDs is of great significance for improving the quality of the birth population and reducing neonatal mortality.This article reviews the research progress in recent years on the occurrence of fetal NTDs caused by abnormal histone modifications mediated by maternal metabolites and provides a prospect for the future research direction.With the aim of revealing the key regulatory function of histone modifications in neural tube development,this review also provides a theoretical basis for further research on the relationship between histone modifications and the occurrence of NTDs,and for the future prevention and treatment strategies of NTDs.
作者
刘增莉
李建婷
刘志贞
LIU Zeng-Li;LI Jian-Ting;LIU Zhi-Zhen(Shanxi Key Laboratory of Birth Defect and Cell Regeneration,Department of Biochemistry and Molecular Biology,School of Basic Medicine,Shanxi Medical University,Taiyuan 030001,China;Key Laboratory of Coal Environmental Pathogenicity and Prevention(Ministry of Education),Shanxi Medical University,Taiyuan 030001,China)
出处
《中国生物化学与分子生物学报》
北大核心
2025年第7期956-966,共11页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金(No.U23A20420,82201841)
山西省基础研究计划(No.202203021212369,202203021221245,202403021221156)
山西医科大学博士启动基金项目(No.SD2209,XD2116)资助。
关键词
神经管畸形
组蛋白修饰
母体代谢物
甲基化
乙酰化
neural tube defects(NTDs)
histone modifications
maternal metabolites
methylation
acetylation
