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Identification of metabolic pathways and key genes associated with atypical parkinsonism using a systems biology approach.
Pasqualotto, Amanda; da Silva, Vinícius; Pellenz, Felipe Mateus; Schuh, Artur Francisco Schumacher; Schwartz, Ida Vanessa Doederlein; Siebert, Marina.
Afiliação
  • Pasqualotto A; Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • da Silva V; BRAIN Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
  • Pellenz FM; Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • Schuh AFS; Serviço de Endocrinologia, -Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil.
  • Schwartz IVD; Graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • Siebert M; Serviço de Neurologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
Metab Brain Dis ; 39(4): 577-587, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38305999
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtornos Parkinsonianos / Biologia de Sistemas / Redes e Vias Metabólicas / Mapas de Interação de Proteínas Tipo de estudo: Diagnostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Metab Brain Dis Assunto da revista: CEREBRO / METABOLISMO Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtornos Parkinsonianos / Biologia de Sistemas / Redes e Vias Metabólicas / Mapas de Interação de Proteínas Tipo de estudo: Diagnostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Metab Brain Dis Assunto da revista: CEREBRO / METABOLISMO Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos