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探索1C代谢的复杂性:对衰老和神经退行性疾病的影响。

Exploring the complexities of 1C metabolism: implications in aging and neurodegenerative diseases.

作者信息

Bou Ghanem Ayman, Hussayni Yaman, Kadbey Raghid, Ratel Yara, Yehya Shereen, Khouzami Lara, Ghadieh Hilda E, Kanaan Amjad, Azar Sami, Harb Frederic

机构信息

Faculty of Medicine and Medical Sciences, University of Balamand, Tripoli, Lebanon.

College of Natural and Health Sciences, Zayed University, Dubai, United Arab Emirates.

出版信息

Front Aging Neurosci. 2024 Jan 4;15:1322419. doi: 10.3389/fnagi.2023.1322419. eCollection 2023.

Abstract

The intricate interplay of one-carbon metabolism (OCM) with various cellular processes has garnered substantial attention due to its fundamental implications in several biological processes. OCM serves as a pivotal hub for methyl group donation in vital biochemical reactions, influencing DNA methylation, protein synthesis, and redox balance. In the context of aging, OCM dysregulation can contribute to epigenetic modifications and aberrant redox states, accentuating cellular senescence and age-associated pathologies. Furthermore, OCM's intricate involvement in cancer progression is evident through its capacity to provide essential one-carbon units crucial for nucleotide synthesis and DNA methylation, thereby fueling uncontrolled cell proliferation and tumor development. In neurodegenerative disorders like Alzheimer's and Parkinson's, perturbations in OCM pathways are implicated in the dysregulation of neurotransmitter synthesis and mitochondrial dysfunction, contributing to disease pathophysiology. This review underscores the profound impact of OCM in diverse disease contexts, reinforcing the need for a comprehensive understanding of its molecular complexities to pave the way for targeted therapeutic interventions across inflammation, aging and neurodegenerative disorders.

摘要

一碳代谢(OCM)与各种细胞过程之间复杂的相互作用因其在多个生物学过程中的重要意义而备受关注。OCM在重要的生化反应中作为甲基供体的关键枢纽,影响DNA甲基化、蛋白质合成和氧化还原平衡。在衰老过程中,OCM失调可导致表观遗传修饰和异常的氧化还原状态,加剧细胞衰老和与年龄相关的病理变化。此外,OCM通过其为核苷酸合成和DNA甲基化提供关键的必需一碳单位的能力,明显参与癌症进展,从而助长不受控制的细胞增殖和肿瘤发展。在阿尔茨海默病和帕金森病等神经退行性疾病中,OCM途径的紊乱与神经递质合成失调和线粒体功能障碍有关,促成疾病的病理生理学。本综述强调了OCM在多种疾病背景下的深远影响,强化了全面理解其分子复杂性的必要性,以便为针对炎症、衰老和神经退行性疾病的靶向治疗干预铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a4/10794399/b113d0a2d9d4/fnagi-15-1322419-g001.jpg

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