Identification of metabolic pathways and key genes associated with atypical parkinsonism using a systems biology approach

• Published in: Metabolic brain disease Vol. 39; no. 4; pp. 577 - 587
• Main Authors: Pasqualotto, Amanda, da Silva, Vinícius, Pellenz, Felipe Mateus, Schuh, Artur Francisco Schumacher, Schwartz, Ida Vanessa Doederlein, Siebert, Marina
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2024; Springer Nature B.V
• Subjects: Alzheimer's disease; Amyloid precursor protein; Animal models; Animals; Apolipoprotein E; Biochemistry; Biological activity; Biology; Biomedical and Life Sciences; Biomedicine; Cell activation; Cognition; Encyclopedias; Enrichment; Gene Regulatory Networks - genetics; Genes; Genomes; Glial cells; Heterogeneity; Humans; Metabolic Diseases; Metabolic Networks and Pathways - genetics; Metabolic pathways; Movement disorders; Neurodegenerative diseases; Neuroglia; Neurology; Neurosciences; Oncology; Original Article; Parkinson's disease; Parkinsonian Disorders - genetics; Parkinsonian Disorders - metabolism; Pathogenesis; Protein interaction; Protein Interaction Maps - genetics; Proteins; Synuclein; Systems Biology; Tau protein; And Lewy body dementia; Multiple system atrophy; Atypical parkinsonism; Systems biology; Progressive supranuclear palsy; Corticobasal degeneration
• ISSN: 1573-7365; 0885-7490; 1573-7365
• DOI: 10.1007/s11011-024-01342-7

Atypical parkinsonism (AP) is a group of complex neurodegenerative disorders with marked clinical and pathophysiological heterogeneity. The use of systems biology tools may contribute to the characterization of hub-bottleneck genes, and the identification of its biological pathways to broaden the understanding of the bases of these disorders. A systematic search was performed on the DisGeNET database, which integrates data from expert curated repositories, GWAS catalogues, animal models and the scientific literature. The tools STRING 11.0 and Cytoscape 3.8.2 were used for analysis of protein-protein interaction (PPI) network. The PPI network topography analyses were performed using the CytoHubba 0.1 plugin for Cytoscape. The hub and bottleneck genes were inserted into 4 different sets on the InteractiveVenn. Additional functional enrichment analyses were performed to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology for a described set of genes. The systematic search in the DisGeNET database identified 485 genes involved with Atypical Parkinsonism. Superimposing these genes, we detected a total of 31 hub-bottleneck genes. Moreover, our functional enrichment analyses demonstrated the involvement of these hub-bottleneck genes in 3 major KEGG pathways. We identified 31 highly interconnected hub-bottleneck genes through a systems biology approach, which may play a key role in the pathogenesis of atypical parkinsonism. The functional enrichment analyses showed that these genes are involved in several biological processes and pathways, such as the glial cell development, glial cell activation and cognition, pathways were related to Alzheimer disease and Parkinson disease. As a hypothesis, we highlight as possible key genes for AP the MAPT (microtubule associated protein tau), APOE (apolipoprotein E), SNCA (synuclein alpha) and APP (amyloid beta precursor protein) genes.