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同型半胱氨酸代谢作为预测性医学方法、疾病预防、预后以及个性化治疗的靶点。

Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person.

作者信息

Koklesova Lenka, Mazurakova Alena, Samec Marek, Biringer Kamil, Samuel Samson Mathews, Büsselberg Dietrich, Kubatka Peter, Golubnitschaja Olga

机构信息

Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia.

Jessenius Faculty of Medicine in Martin, Biomedical Centre Martin, Comenius University in Bratislava, Mala Hora 4D, 036 01 Martin, Slovakia.

出版信息

EPMA J. 2021 Nov 11;12(4):477-505. doi: 10.1007/s13167-021-00263-0. eCollection 2021 Dec.

Abstract

Homocysteine (Hcy) metabolism is crucial for regulating methionine availability, protein homeostasis, and DNA-methylation presenting, therefore, key pathways in post-genomic and epigenetic regulation mechanisms. Consequently, impaired Hcy metabolism leading to elevated concentrations of Hcy in the blood plasma (hyperhomocysteinemia) is linked to the overproduction of free radicals, induced oxidative stress, mitochondrial impairments, systemic inflammation and increased risks of eye disorders, coronary artery diseases, atherosclerosis, myocardial infarction, ischemic stroke, thrombotic events, cancer development and progression, osteoporosis, neurodegenerative disorders, pregnancy complications, delayed healing processes, and poor COVID-19 outcomes, among others. This review focuses on the homocysteine metabolism impairments relevant for various pathological conditions. Innovative strategies in the framework of 3P medicine consider Hcy metabolic pathways as the specific target for in vitro diagnostics, predictive medical approaches, cost-effective preventive measures, and optimized treatments tailored to the individualized patient profiles in primary, secondary, and tertiary care.

摘要

同型半胱氨酸(Hcy)代谢对于调节蛋氨酸可用性、蛋白质稳态和DNA甲基化至关重要,因此是后基因组和表观遗传调控机制中的关键途径。因此,Hcy代谢受损导致血浆中Hcy浓度升高(高同型半胱氨酸血症)与自由基的过度产生、诱导的氧化应激、线粒体损伤、全身炎症以及眼部疾病、冠状动脉疾病、动脉粥样硬化、心肌梗死、缺血性中风、血栓形成事件、癌症发展和进展、骨质疏松症、神经退行性疾病、妊娠并发症、愈合过程延迟以及COVID-19不良预后等风险增加有关。本综述重点关注与各种病理状况相关的同型半胱氨酸代谢损伤。3P医学框架内的创新策略将Hcy代谢途径视为体外诊断、预测性医学方法、具有成本效益的预防措施以及针对初级、二级和三级护理中个体化患者档案量身定制的优化治疗的特定靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a2/8648914/eec7abe220f6/13167_2021_263_Fig1_HTML.jpg

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