Meta-Analysis of Parkinson’s Disease and Alzheimer’s Disease Revealed Commonly Impaired Pathways and Dysregulation of NRF2-Dependent Genes
Abstract
Many lines of evidence suggest that Parkinson's disease (PD) and Alzheimer's disease (AD) have common characteristics, such as mitochondrial dysfunction and oxidative stress. As the underlying molecular mechanisms are unclear, we perform a meta-analysis with 9 microarray datasets of PD studies and 7 of AD studies to explore it. Functional enrichment analysis revealed that PD and AD both showed dysfunction in the synaptic vesicle cycle, GABAergic synapses, phagosomes, oxidative phosphorylation, and TCA cycle pathways, and AD had more enriched genes. Comparing the differentially expressed genes between AD and PD, we identified 54 common genes shared by more than six tissues. Among them, 31 downregulated genes contained the antioxidant response element (ARE) consensus sequence bound by NRF2. NRF2 is a transcription factor, which protects cells against oxidative stress through coordinated upregulation of ARE-driven genes. To our surprise, although NRF2 was upregulated, its target genes were all downregulated. Further exploration found that MAFF was upregulated in all tissues and significantly negatively correlated with the 31 NRF2-dependent genes in diseased conditions. Previous studies have demonstrated over-expressed small MAFs can form homodimers and act as transcriptional repressors. Therefore, MAFF might play an important role in dysfunction of NRF2 regulatory network in PD and AD.
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Downregulation of Nrf2-target genes has been reported in Alzheimer's disease and other neurodegenerative conditions.
“Downregulation of Nrf2-target genes have been reported in AD, and other neurodegenerative conditions [112].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [112]
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Self-citation
- Authors
- Wang, Q., Li, W.-X., Dai, S.-X., Guo, Y.-C., Han, F.-F., Zheng, J.-J., Li, G.-H., & Huang, J.-F.
- Affiliations
- Kunming Institute of Zoology (CN)
- State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China
- Harvard University (US)
- Chinese University of Hong Kong (HK)
- Corresponding author
- Li, Gong-Hua
- Huang, Jing-Fei
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2017-02-07
- Volume
- 56
- Issue
- 4
- Pages
- 1525-1539
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2586975540
- Cited by
- 88
- References
- 67
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 6 · 2023: 4 · 2022: 13 · 2021: 21 · 2020: 12 · 2019: 10 · 2018: 4 · 2017: 3
- FWCI
- 1.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Brain, Humans, Nuclear Proteins, Parkinson Disease, Signal Transduction, MafF Transcription Factor, NF-E2-Related Factor 2
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