Functional analysis and signaling pathway enrichment analysis of genes associated with Alzheimer's disease and Parkinson's disease

We identified significant functions of susceptibility-genes and performed an analysis of pathway enrichment for Alzheimer's disease, Parkinson's disease and for both of them. Genes were extracted from a Catalog of Published Genome-Wide Association Studies (GWAS). We uploaded genes into Cytoscape version 3.2.1. ClueGO plugin was used for functional and pathway enrichment analysis of genes based on the hypergeometric test. Two databases, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and REACTOME, were selected for analysis. The identified susceptibility genes are involved in the synthesis regulation and accumulation of toxic proteins, beta-amyloid and alpha-synuclein, and lead to apoptosis of neurons. We have defined 14 shared functions: collagen catabolic process, cellular response to retinoic acid, regulation of calcium-mediated signaling, negative regulation of cell projection organization, negative regulation of neuron projection development, glial cell activation, microglial cell activation, macrophage activation, regulation of cholesterol metabolism, clathrin-mediated endocytosis, regulation of protein oligomerization, regulation of dendritic spine development, kinesin binding and clathrin binding. Also, we have defined 3 shared signaling pathways: trans-Golgi Network Vesicle Budding, Clathrin derived vesicle budding, Intestinal immune network for IgA production. These pathways contain genes susceptible to Alzheimer's disease and Parkinson's disease. The results suggest the metabolic, neuronal and immunological factors participate in the development of Parkinson's disease and Alzheimer's disease.