Considerable evidence suggests that metabolic abnormalities are associated with neurodegenerative diseases. This study aimed to conduct a systematic metabolic analysis of Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). Human and mouse model microarray datasets were downloaded from the Gene Expression Omnibus database. The metabolic genes and pathways were collected from the Recon 3D human metabolic model. Drug and target information was obtained from the DrugBank database. This study identified ATP1A1, ATP6V1G2, GOT1, HPRT1, MAP2K1, PCMT1 and PLK2 as key metabolic genes that were downregulated in AD, PD and HD. We screened 57 drugs that target these genes, such as digoxin, ouabain and diazoxide. This study constructed multigene diagnostic models for AD, PD and HD by using metabolic gene expression profiles in blood, all models showed high accuracy (AUC > 0.8) both in the experimental and validation sets. Furthermore, analysis of animal models showed that there was almost no consistency among the metabolic changes between mouse models and human diseases. This study systematically revealed the metabolic damage among AD, PD, and HD and uncovered the differences between animal models and human diseases. This information may be helpful for understanding the metabolic mechanisms and drug development for neurodegenerative diseases.

中文翻译：

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对三种神经退行性疾病的潜在靶标，治疗药物，诊断方法和动物模型适用性进行系统代谢分析。

大量证据表明，代谢异常与神经退行性疾病有关。这项研究旨在对阿尔茨海默氏病（AD），帕金森氏病（PD）和亨廷顿氏病（HD）进行系统的代谢分析。从Gene Expression Omnibus数据库下载了人类和小鼠模型微阵列数据集。代谢基因和途径是从Recon 3D人类代谢模型中收集的。药物和靶标信息是从DrugBank数据库获得的。这项研究确定了ATP1A1，ATP6V1G2，GOT1，HPRT1，MAP2K1，PCMT1和PLK2作为在AD，PD和HD中下调的关键代谢基因。我们筛选了针对这些基因的57种药物，例如地高辛，哇巴因和重氮。这项研究通过使用血液中的代谢基因表达谱构建了AD，PD和HD的多基因诊断模型，所有模型在实验组和验证组中均显示出较高的准确性（AUC> 0.8）。此外，对动物模型的分析表明，小鼠模型与人类疾病之间的代谢变化之间几乎没有一致性。这项研究系统地揭示了AD，PD和HD之间的代谢损伤，并揭示了动物模型与人类疾病之间的差异。这些信息可能有助于理解神经退行性疾病的代谢机制和药物开发。