Differential gene expression by RNA-seq during Alzheimer's disease-like progression in the Drosophila melanogaster model.

Autor: da Costa Silva JR; Laboratory of Genetics, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Fujimura PT; Laboratory of Genetics, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Batista LL; Laboratory of Genetics, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Malta SM; Laboratory of Genetics, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Filho RM; Laboratory of Genetics, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Silva MH; Laboratory of Genetics, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., de Souza AG; Laboratory of Genetics, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Silva APM; Department of Molecular Brain Science at the Centre for Addiction and Mental Health (CAMH), Canada., Borges LDF; Laboratory of Genetics, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Bastos VAF; Laboratory of Genetics, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Cossolin JFS; Department of General Biology, Federal University of Viçosa, Viçosa, MG, Brazil., Serrão JE; Department of General Biology, Federal University of Viçosa, Viçosa, MG, Brazil., Bonetti AM; Laboratory of Genetics, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Júnior LCO; Laboratory of Genetics, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil; Faculty of Medicine, Federal University of Uberlandia, Uberlandia, MG, Brazil., Ueira-Vieira C; Laboratory of Genetics, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil. Electronic address: ueira@ufu.br.
Jazyk: angličtina
Zdroj: Neuroscience research [Neurosci Res] 2022 Jul; Vol. 180, pp. 1-12. Date of Electronic Publication: 2022 Feb 24.
DOI: 10.1016/j.neures.2022.02.003
Abstrakt: Alzheimer's disease (AD) is characterized by progressive, irreversible loss of memory and cognitive function. Drosophila melanogaster and other animal models are used to study several diseases, in order to elucidate unknown mechanisms and develop potential therapies. Molecular studies require biological samples and, for neuropathologies such as AD biopsy of the human brain, are invasive and potentially damaging. The solution is to use animal models, such as D. melanogaster, which is a model organism that can replace mammalian organisms in such studies. In this study, we evaluated the climbing ability and differential gene expression during AD progression due to the amylodoigenic pathway using RNA-seq, and we performed an in silico analysis of a fruit fly AD-like GFP (Green Fluorescent Protein) model with GFP expression in the pan-neural elav driver. A total of 1388 genes were differentially expressed in all analyzed groups. The main pathways related to those Differentially Expressed Genes (DEGs) during aging and AD progression were evaluated using the fly genes and human orthologs, in order to link genomic information to higher-order functional information with gene pathway mapping. We identified pathways present in all analyzed groups, such as metabolic pathways, ribosomal pathways, proteasome pathways and immune system pathways. Some of the genes were validated by qPCR. Knockdown of CG17754 gene by RNAi promoted degeneration in the fly eye, validating these findings in vivo. The identification of similarities in molecular pathways between the transgenic fly AD-like GFP model and mammals related to AD provides new insights into the use of this fly in screening novel anti-AD drugs.
(Copyright © 2022 Japan Neuroscience Society and Elsevier B.V. All rights reserved.)
Databáze: MEDLINE