Research Paper Volume 12, Issue 10 pp 9882—9914
Systematic metabolic analysis of potential target, therapeutic drug, diagnostic method and animal model applicability in three neurodegenerative diseases
- 1 Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
- 2 Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, Yunnan, China
- 3 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
- 4 Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, Yunnan, China
- 5 Centre for Excellence in Brain Science and Intelligent Technology, Chinese Academy of Sciences, Shanghai 200031, China
Received: February 25, 2020 Accepted: April 20, 2020 Published: May 27, 2020
https://doi.org/10.18632/aging.103253How to Cite
Copyright © 2020 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.