关键词: 神经管畸形, 高同型半胱氨酸血症, DNA甲基化, 氧化应激

Abstract: Neural tube defects (NTDs) are one of the most common central nervous system defects in newborns. Neural plate development, neural plate shape, neural plate curling, and nerve fold fusion are the four stages of neural tube closure, where genetic and environmental risk factors are involved. Through oxidative stress, Ca²⁺ overload, and a decreased S-adenosyl methionine(SAM)/S-adenosylhomocysteine(SAH) ratio, hyperhomocysteinemia(HHcy) causes overall DNA hypomethylation in the embryo, which results in high expression of genes involved in neural tube closure through histone modifications, gene polymorphisms, and methionine synthetase(MTR), as well as the activation of related signaling pathways(such as the Wnt/β-catenin signaling pathway and the PI3K/AKT signaling pathway), impairing the proper development of the neural tube, upsetting the equilibrium between cell proliferation and apoptosis, ultimately resulting in NTDs. Using data from earlier studies, this review strengthens the correlation between HHcy and NTDs, offers a theoretical framework for clinical NTD diagnosis and prevention, and goes into greater detail about the aforementioned pathways and their connection to HHcy.

Key words: neural tube defects, hyperhomocysteinemia, DNA methylation, oxidative stress