Appearance
question:Lanke, V and Moolamalla, STR and Roy, D and Vinod, PK (2018) Integrative Analysis of Hippocampus Gene Expression Profiles Identifies Network Alterations in Aging and Alzheimer’s Disease. Front Aging Neurosci, 10 (153). Alzheimer’s disease (AD) is a neurodegenerative disorder contributing to rapid decline in cognitive function and ultimately dementia. Most cases of AD occur in elderly and later years. There is a growing need for understanding the relationship between aging and AD to identify shared and unique hallmarks associated with the disease in a region and cell-type specific manner. Although genomic studies on AD have been performed extensively, the molecular mechanism of disease progression is still not clear. The major objective of our study is to obtain a higher-order network-level understanding of aging and AD, and their relationship using the hippocampal gene expression profiles of young (20–50 years), aging (70–99 years), and AD (70–99 years). The hippocampus is vulnerable to damage at early stages of AD and altered neurogenesis in the hippocampus is linked to the onset of AD. We combined the weighted gene co-expression network and weighted protein–protein interaction network-level approaches to study the transition from young to aging to AD. The network analysis revealed the organization of co-expression network into functional modules that are cell-type specific in aging and AD. We found that modules associated with astrocytes, endothelial cells and microglial cells are upregulated and significantly correlate with both aging and AD. The modules associated with neurons, mitochondria and endoplasmic reticulum are downregulated and significantly correlate with AD than aging. The oligodendrocytes module does not show significant correlation with neither aging nor disease. Further, we identified aging- and AD-specific interactions/subnetworks by integrating the gene expression with a human protein–protein interaction network. We found dysregulation of genes encoding protein kinases (FYN, SYK, SRC, PKC, MAPK1, ephrin receptors) and transcription factors (FOS, STAT3, CEBPB, MYC, NFKβ, and EGR1) in AD. Further, we found genes that encode proteins with neuroprotective function (14-3-3 proteins, PIN1, ATXN1, BDNF, VEGFA) to be part of the downregulated AD subnetwork. Our study highlights that simultaneously analyzing aging and AD will help to understand the pre-clinical and clinical phase of AD and aid in developing the treatment strategies. Can you explain the relationship between aging and Alzheimer's disease using the hippocampal gene expression profiles?
answer:The relationship between aging and Alzheimer’s disease (AD) was explored using hippocampal gene expression profiles, focusing on young, aging, and AD age groups. The hippocampus is crucial to study as it is vulnerable to damage in the early stages of AD, and altered neurogenesis can be observed in this region. A combination of weighted gene co-expression network and weighted protein-protein interaction network-level approaches were utilized to identify functional modules that are cell-type specific in aging and AD. Furthermore, interactions and subnetworks were identified by integrating gene expression data with a human protein-protein interaction network. The study found that modules associated with astrocytes, endothelial cells, and microglial cells are upregulated and significantly correlate with both aging and AD. Conversely, modules associated with neurons, mitochondria, and endoplasmic reticulum are downregulated and significantly correlate with AD more than with aging. Interestingly, the oligodendrocytes module does not show a significant correlation with either aging or disease. The study suggests that focusing on aging and AD together can aid in understanding the pre-clinical and clinical phases of AD and help develop treatment strategies. The study also identified dysregulated genes encoding protein kinases and transcription factors, as well as downregulated genes encoding proteins with neuroprotective functions, giving insight into the molecular mechanisms of disease progression.
question:Can you please provide a summary of the main findings of the study?
answer:The study analyzed hippocampus gene expression profiles of young, aging, and Alzheimer's disease (AD) patients using a weighted gene co-expression network and protein-protein interaction network approach. The study found that modules associated with astrocytes, endothelial cells, and microglial cells are upregulated and significantly correlate with both aging and AD, whereas modules associated with neurons, mitochondria, and endoplasmic reticulum are downregulated and significantly correlate with AD but not aging. Genes encoding protein kinases and transcription factors were found to be dysregulated in AD, and genes encoding proteins with neuroprotective functions were downregulated in AD. The study highlights the importance of analyzing aging and AD together to aid in understanding the pre-clinical and clinical phases of AD and developing treatment strategies.
question:Can you tell me more about the specific protein kinases and transcription factors that were found to be dysregulated in AD?
answer:The study identified several protein kinases and transcription factors that were dysregulated in AD. These dysregulated genes include FYN, SYK, SRC, PKC, MAPK1, ephrin receptors, FOS, STAT3, CEBPB, MYC, NFKβ, and EGR1. FYN, SYK, SRC, and PKC are all protein kinases that are involved in various signaling pathways related to neurodegeneration. MAPK1 (mitogen-activated protein kinase 1) is a protein kinase involved in many cellular processes, and its dysregulation has been implicated in AD. Ephrin receptors are also involved in various signaling pathways, including regulation of synaptic plasticity, and have been found to be dysregulated in AD. FOS, STAT3, CEBPB, MYC, NFKβ, and EGR1 are transcription factors that are involved in transcriptional regulation and have been implicated in AD pathogenesis. Dysregulation of these proteins suggests that they may play a role in the molecular mechanisms underlying AD.
question:How will the Marketing Executive collaborate with the Head of Marketing and what opportunities for creativity and campaign development will they have? Answer according to: To assist the Head of Marketing with all aspects of Frontier’s media marketing channels and to ensure an excellent web presence. Frontier has been offering responsible travel opportunities since 1989. With projects across the globe in countries including Madagascar, Costa Rica, Fiji and Belize, we are the leading provider of conservation and community travel experiences. Based at our HQ in Shoreditch, London, the Marketing Executive will work with the Head of Marketing and other colleagues in the marketing department to reach out to more travellers and enhance the company’s brand. There will be a number of existing campaigns for the Marketing Executive to develop, as well as plenty of scope to implement and develop their own ideas.
answer:The Marketing Executive will collaborate closely with the Head of Marketing in order to execute effective and innovative marketing campaigns. They will work together to set goals and create strategies for reaching those goals, as well as monitor and analyse the success of those campaigns. The Marketing Executive will also have the opportunity to contribute their own ideas and creativity to the company’s marketing efforts. They will have the chance to develop new campaigns and initiatives that align with Frontier’s values and brand, and that will attract even more travellers to the company. Overall, the Marketing Executive will work closely with the Head of Marketing and other colleagues in order to ensure that Frontier’s media marketing channels are effective and that the company has a strong web presence. They will have plenty of opportunities to use their creativity, develop campaigns, and contribute to the growth of the company.