The study is based on the complexity of Insulin like growth factor receptor (IGF1R) signaling and its regulation by noncoding RNAs (ncRNAs). IGF1R signaling is an important cascade in Alzheimer's disease (AD); however, its regulation and roles are poorly understood. Due to the presence of ß-arrestin and GPCR Receptor Kinase binding sites, this protein has been termed a 'functional hybrid', as it can take part in both kinase and GPCR signaling pathways, further adding to its complexity. The objective of this study is to understand the underlying ncRNA regulation controlling IGF1R and GPCRs in AD to find commonalities in the network. We found through data mining that 45 GPCRs were reportedly deregulated in AD and built clusters based on GO/KEGG pathways to show shared functionality with IGF1R. Eight miRs were further discovered that could coregulate IGF1R and GPCRs. We validated their expression in an AD cell model and probed for common lncRNAs downstream that could regulate these miRs. Seven such candidates were identified and further validated. A combined network comprising IGF1R with nine GPCRs, eight miRs, and seven lncRNAs was created to visualize the interconnectivity within pathways. Betweenness centrality analysis showed a cluster of NEAT1, hsa-miR-15a-5p, hsa-miR-16-5p, and IGF1R to be crucial form a competitive endogenous RNA-based (ceRNA) tetrad that could relay information within the network, which was further validated by cell-based studies. NEAT1 emerged as a master regulator that could alter the levels of IGF1R and associated GPCRs. This combined bioinformatics and experimental study for the first time explored the regulation of IGF1R through ncRNAs from the perspective of neurodegeneration.
Alzheimer Disease , MicroRNAs , RNA, Long Noncoding , Receptor, IGF Type 1 , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Humans , Receptor, IGF Type 1/genetics , Receptor, IGF Type 1/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Signal Transduction/genetics , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Gene Expression Regulation , Receptors, Somatomedin/genetics , Receptors, Somatomedin/metabolism , Gene Regulatory Networks
Single-use plastic (SUP) being a versatile material, is adopted as an alternate to traditional materials specifically for the use in food packaging due to its inherent characteristics like high durability, inertness, and protecting ability but has become a curse for living being today due to its random usage and unplanned rejection to nature. Mostly plastics used in packaging of beverages, fresh meats, fruits and vegetables are under concern today. Single-use packages result in generation of several billion tons of garbage till date, which pollutes the environment. At the immediate past, it has come to light that micro plastics obtained due to slow degradation of SUP present in oceans, are also being consumed by marine organisms such as fishes and shellfish species which disturbs the marine life extensively. Hence, finding right strategy to mitigate the plastic waste related issues has becoming inevitable today. This review paper briefs various strategies undertaken worldwide to mitigate the pollution due to generation of plastic waste. Various notable impact of adopted strategies and recent innovations to replace the SUP products are also discussed and in view of this a roadmap is also suggested which can be used to achieve the milestone of Zero Plastic Waste.
