ABSTRACT
The process of ageing accompanies several metabolic diseases. With ageing, fats accumulate to increase the visceral and abdominal adiposity leading to hyperinsulinemia, insulin resistance, obesity and several other diseases. Drosophila melanogaster is often used to study the ageing process and its related disorders. Therefore, in this study, we performed an in silico analysis to relate the process of ageing and insulin resistance. We analysed the data of insulin-resistant Drosophila from the GEO database and compared it with the data from the literature survey. We observed that 98 genes were common in both the models, and they showed gene modulations related to metabolic pathways, fatty acid metabolism, insulin resistance and neural receptor-ligand binding pathways. Analysis of the REACTOME database against human data revealed that the TRKB signalling pathway is commonly affected. The TRKB-mediated BDNF pathway is a major regulator of memory loss. We further analysed the common genes in Alzheimer's disease and compared the fly data with human data to identify the diseases related to these common genes. Then, we performed a literature survey to provide protective mechanisms for the TRKB signalling pathway activation, mediated through polyphenols. We treated the flies with sesamol-conjugated lipoic acid derivative (a phenolic compound) at hormetic doses to evaluate its effect on the memory of flies.
Subject(s)
Aging/genetics , Alzheimer Disease/genetics , Insulin Resistance/genetics , Obesity/genetics , Aging/metabolism , Alzheimer Disease/metabolism , Animals , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster , Genome, Human , Genome, Insect , Humans , Obesity/metabolism , Receptor, trkB/genetics , Receptor, trkB/metabolism , Signal TransductionABSTRACT
Deletion of tumor suppressor gene, lethal(2)giant larvae [l(2)gl], leads to brain tumor in Drosophila melanogaster at larval stage of development and severe brain dysplasia in mice. We have studied the effect of two potential antitumor drugs artemisinin and curcumin in the perspective of inhibiting l(2)gl brain tumor. Efficacies of these drugs are characterized morphologically by measuring brain sizes of untreated and treated larvae on the basis of tumor inhibition and anatomically by looking at the cellular patterning via antibody staining of the third instar Drosophila larval brains. Behavioral experiments were done in form of locomotion to correlate tumor inhibition with the revival of brain function and longevity assays to assess general health span. It was observed that both drugs show antitumor properties individually and in combination when larvae were treated with these drugs. We also found evidence for reactive oxygen species-mediated action of these drugs. Both the drugs when treated individually or together show better median life span and locomotory response. Although the efficacies of various treatments varied, overall, the positive effects of artemisinin and curcumin demonstrate a potential applicability of these drugs against brain tumor in higher organisms. It also paves a way for a simpler model system for screening such natural products for antitumor property.
