title: 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.
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.|Institute of Health Sciences, Anhui University, Hefei, Anhui, China.
authors.forename: Wen-Xing
authors.initials: WX
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Shao-Xing
authors.initials: SX
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Guo
authors.affiliation: Immuno-Metabolic Computational Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Han
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Jun-Juan
authors.initials: JJ
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Gong-Hua
authors.initials: GH
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.|KIZ-SU Joint Laboratory of Animal Models and Drug Development, College of Pharmaceutical Sciences, Soochow University, Kunming, Yunnan, China.|Collaborative Innovation Center for Natural Products and Biological Drugs of Yunnan, Kunming, Yunnan, China.|Chinese University of Hong Kong Joint Research Center for Bio-resources and Human Disease Mechanisms, Kunming, Yunnan, China.
authors.forename: Jing-Fei
authors.initials: JF
authors.lastname: Huang
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D006801:Humans; D051260:MafF Transcription Factor / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C484147:MAFF protein, human; D051260:MafF Transcription Factor; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009687:Nuclear Proteins
keywords: Alzheimer’s disease; MAFF; NRF2; Parkinson’s disease; meta-analysis