Hypoxia, that is, an inadequate oxygen supply, is linked to neurodegeneration and patients with cardiovascular disease are prone to Alzheimer's disease (AD). 2-Oxoglutarate and ferrous iron-dependent oxygenases (2OGDD) play a key role in the regulation of oxygen homeostasis by acting as hypoxia sensors. 2OGDD also have roles in collagen biosynthesis, lipid metabolism, nucleic acid repair, and the regulation of transcription and translation. Many biological processes in which the >60 human 2OGDD are involved are altered in AD patient brains, raising the question as to whether 2OGDD are involved in the transition from normal aging to AD. Here we give an overview of human 2OGDD and critically discuss their potential roles in AD, highlighting possible relationships with synapse dysfunction/loss. 2OGDD may regulate neuronal/glial differentiation through enzyme activity-dependent mechanisms and modulation of their activity has potential to protect against synapse loss. Work linking 2OGDD and AD is at an early stage, especially from a therapeutic perspective; we suggest integrated pathology and in vitro discovery research to explore their roles in AD is merited. We hope to help enable long-term research on the roles of 2OGDD and, more generally, oxygen/hypoxia in AD. We also suggest shorter term empirically guided clinical studies concerning the exploration of 2OGDD/oxygen modulators to help maintain synaptic viability are of interest for AD treatment.

中文翻译：

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探索 2-酮戊二酸依赖性加氧酶与阿尔茨海默病之间的联系

缺氧，即氧气供应不足，与神经退行性疾病有关，患有心血管疾病的患者容易患阿尔茨海默病 (AD)。2-氧戊二酸和二价铁依赖性加氧酶 (2OGDD) 作为缺氧传感器，在氧稳态调节中发挥着关键作用。2OGDD 还在胶原蛋白生物合成、脂质代谢、核酸修复以及转录和翻译调节中发挥作用。AD 患者大脑中涉及超过 60 个人类 2OGDD 的许多生物过程发生了改变，这就提出了 2OGDD 是否参与从正常衰老到 AD 的转变的问题。在这里，我们概述了人类 2OGDD，并批判性地讨论了它们在 AD 中的潜在作用，强调了与突触功能障碍/丧失的可能关系。2OGDD 可能通过酶活性依赖性机制调节神经元/胶质细胞分化，并且对其活性的调节有可能防止突触损失。连接 2OGDD 和 AD 的工作还处于早期阶段，特别是从治疗的角度来看；我们建议综合病理学和体外发现研究来探索它们在 AD 中的作用是值得的。我们希望帮助开展关于 2OGDD 以及更广泛的氧气/缺氧在 AD 中的作用的长期研究。我们还建议，关于探索 2OGDD/氧调节剂以帮助维持突触活力的短期经验指导临床研究对于 AD 治疗很有意义。