Gupta Parul, Kumar Ravindra
ICMR-National Institute of Research in Tribal Health, India.
ICMR-National Institute of Research in Tribal Health, India.
Gene. 2023 Dec 20;888:147749. doi: 10.1016/j.gene.2023.147749. Epub 2023 Aug 29.
GCH1 gene provides directions for the synthesis of GTP cyclohydrolase 1 which regulates the formation of Tetrahydrobiopterin (BH4). BH4 is a crucial cofactor for essential neurotransmitters synthesis such as dopamine, serotonin and nitric oxide synthases. Deficiency of GCH1 limits the synthesis of BH4 which is responsible for neuropsychiatric diseases such as dopa-responsive dystonia, hyperalaninemia, Parkinson's disease and depression. Few single nucleotide polymorphisms of GCH1 gene are also responsible for pain in sickle cell disease. Furthermore, GCH1 regulates NO activity which controls the blood pressure, vasodilatory functions and oxidative stress. Understanding the therapeutic implications of targeting GCH1 which holds promise for treating various diseases. Novel therapeutic strategies could involve small molecule drugs or gene therapy techniques that enhance GCH1 expression or activity.
GCH1基因指导合成鸟苷三磷酸环化水解酶1，该酶调节四氢生物蝶呤（BH4）的形成。BH4是多巴胺、血清素和一氧化氮合酶等必需神经递质合成的关键辅助因子。GCH1缺乏会限制BH4的合成，而这与多巴反应性肌张力障碍、高丙氨酸血症、帕金森病和抑郁症等神经精神疾病有关。GCH1基因的少数单核苷酸多态性也与镰状细胞病的疼痛有关。此外，GCH1调节一氧化氮活性，而一氧化氮控制血压、血管舒张功能和氧化应激。了解靶向GCH1的治疗意义有望治疗各种疾病。新的治疗策略可能涉及增强GCH1表达或活性的小分子药物或基因治疗技术。
