PDF(Pubmed)
Abstract：
Vitamin B12 (VitB12) is a micronutrient and acts as a cofactor for fundamental biochemical reactions: the synthesis of succinyl-CoA from methylmalonyl-CoA and biotin, and the synthesis of methionine from folic acid and homocysteine. VitB12 deficiency can determine a wide range of diseases, including nervous system impairments. Although clinical evidence shows a direct role of VitB12 in neuronal homeostasis, the molecular mechanisms are yet to be characterized in depth. Earlier investigations focused on exploring the biochemical shifts resulting from a deficiency in the function of VitB12 as a coenzyme, while more recent studies propose a broader mechanism, encompassing changes at the molecular/cellular levels. Here, we explore existing study models employed to investigate the role of VitB12 in the nervous system, including the challenges inherent in replicating deficiency/supplementation in experimental settings. Moreover, we discuss the potential biochemical alterations and ensuing mechanisms that might be modified at the molecular/cellular level (such as epigenetic modifications or changes in lysosomal activity). We also address the role of VitB12 deficiency in initiating processes that contribute to nervous system deterioration, including ROS accumulation, inflammation, and demyelination. Consequently, a complex biological landscape emerges, requiring further investigative efforts to grasp the intricacies involved and identify potential therapeutic targets.
摘要：
维生素B12（VitB12）是一种微量营养素，可作为基本生化反应的辅因子：由甲基丙二酰辅酶A和生物素合成琥珀酰辅酶A，以及由叶酸和高半胱氨酸合成蛋氨酸。VitB12缺乏可以决定多种疾病，包括神经系统损伤.尽管临床证据表明VitB12在神经元稳态中具有直接作用,分子机制尚未深入表征。早期的研究集中在探索由于VitB12作为辅酶的功能缺陷而导致的生化变化。虽然最近的研究提出了更广泛的机制，包括分子/细胞水平的变化。这里,我们探索用于研究VitB12在神经系统中的作用的现有研究模型，包括在实验环境中复制缺陷/补充所固有的挑战。此外，我们讨论了潜在的生化改变和随后可能在分子/细胞水平上被修饰的机制(如表观遗传修饰或溶酶体活性的改变).我们还讨论了VitB12缺乏在引发神经系统恶化过程中的作用，包括ROS积累，炎症,和脱髓鞘.因此,复杂的生物景观出现了，需要进一步的调查努力，以掌握所涉及的复杂性，并确定潜在的治疗目标。
