| Alzheimer's disease(AD)is a progressive development of lethal neurodegenerative disease,with the following clinical manifestations: the deterioration of cognition and memory;progressive ability of daily living and a variety of neuropsychiatric symptoms and behavioral disorders.With the development of society,the aging of our population is increasing,and the prevalence of AD gradually increased,which has brought a heavy burden to the family and society.The pathogenesis of AD has not been revealed so far,and it is generally considered to be the result of a combination of genetic,environmental and other multiple factors.In recent years,with the rapid development of life sciences,especially the extensive application of various omics techniques,which produces a lot of high-throughput biological data,and this provides a new way of thinking and research for further study and understanding of the occurrence and development of complex diseases(including AD).Currently,the use of bioinformatics and systems biology research strategies and methods to integrate data at all levels,and reasonably and effectively analyzed the data,which is of great significance for further elucidating the molecular mechanism of AD and its treatment.On one hand,our study started from the AD-related genes which has been reported,used a variety of data resources,combined with the computational system biology analysis method,built AD feature network,and analyzed the vital functional modules,and predicted the new AD-related genes.On the other hand,our study used ionomics research methods,deeply discussed the characteristic spectrum of mineral elements in the process of AD development.And initially revealed the potential mechanism of sodium selenate intervention in AD transgenic mice.The main research work includes:(1)A comprehensive database of AD related genes was constructed,the ADspecific protein interaction network was established,deeply diggedthe important modules,and the new AD-related genes were predicted.We read a lot of literature and other existing information to create a more comprehensive AD-related gene database,including 1132 AD related genes.To our knowledge,it is the most comprehensive AD relatedgene database.Through the analysis offunctional enrichment,we find that the proteins encoded by AD-related genes are significantly associated with NADH dehydrogenase activity,oxidoreductase activity,enzyme binding capacity,and receptor binding capacity.The proteins encoded by AD-related genes are closely related with energy metabolism,respiratory electron transfer,ATP synthesis and uncoupling protein heat generation and other metabolic pathways.On the basis of the database we have got,we used a variety of human brain gene expression datasets in Allen Brian Atlas(ABA),which is currently the largest total gene expression database,combined with weighted gene coexpression network analysis,we have identified a number of ADknown genes that are enriched by important functional modules and predicted several potential AD-related genes.These results provide useful information for further understanding of the complex molecular mechanisms underlying the development of AD.(2)We revealed the characteristics of mineral elements in the development of AD at the level of ionomics and explored the potential new mechanism of sodium selenate intervention in AD transgenic mice.We used wild-type mouse(WT)and AD three transgenic model mice(3×Tg-AD),through the addition of with/without high-dose sodium selenate,carried out multi-group time points of ion group detection and analysis,we studied the changes in the concentration of 15 elements in the brain and their interactions.The results showed that most of the elements that may become AD risk factors are significantly reduced after 6 months of sodium selenate supplementation,especially iron,whose level is largely reversed to normal in the early stages.Elemental correlation analysis showed that long-term supplementation with sodium selenate could alter the complex dynamic relationship between selenium and other elements,and some changes in the relationship may be closely related to the remission of AD symptoms.The study could help us understand the potential new mechanism of sodium selenate intervention in AD. |
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