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The identification of dysfunctional crosstalk of pathways in Parkinson disease
Authors:Hongyu Diao  Xinxing Li  Sheng Hu
Institution:1. Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China;2. Department of Neurosurgery, The Second People''s Hospital of Chaoyang City, Chaoyang, 122000, China
Abstract:Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting 1–2% of the population over the age of 65. Both genetic and environmental factors trigger risks of and protection from PD. However, the molecular mechanism of PD is far from being clear. In this study, we downloaded the gene expression profile of PD from Gene Expression Omnibus and identified differentially expressed genes (DEGs) and dysfunctional pathways in PD patients compared with controls. To further understand how these pathways act together to account for the initiation of PD, we constructed a pathway crosstalk network by calculating the Jaccard index among pathways. A total of 873 DEGs and 16 dysfunctional pathways between PD patients and controls were identified. Through constructing a network of pathways, the relationships among PD pathways were visually presented by their interactions. Our results demonstrate the existence of crosstalk between different pathways in PD pathogenesis. These results not only may explain the causes of PD, but could also open the door to new therapeutic approaches for this disease.
Keywords:PD  Parkinson disease  DEGs  differentially expressed genes  LRRK2  leucine-rich repeat kinase 2  PINK1  PTEN-induced putative kinase 1  PARK  parkin  GBA  glucocerebrosidase  UCHL1  ubiquitin carboxyl-terminal esterase L1  SNCA  alpha-synuclein  GEO  Gene Expression Omnibus  KEGG  Kyoto Encyclopedia of Genes and Genomes  RMA  robust multi-array average  FDR  false discovery rate  DA  dopamine  LTP  long-term potentiation  SV  synaptic vesicles
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