Construction And Analysis Of MiRNA-Gene Regulatory Network And Time Delay Dynamics Model Associated With Alzheimer’s Disease

Alzheimer’s disease(AD)is a chronic neurodegenerative disease,and its pathogenesis is complex.Currently,there is no cure for the disease and most drugs can only delay the occurrence of the disease.Studies have shown that the occurrence of AD involves complex biological processes and physiological lesions.Heredity,extracellular Aβ amyloid plaques,hyperphosphorylated tau protein tangles have all been confirmed to be related to the pathogenesis of AD,but the key factors causing AD have not been conclusively explained.Therefore,exploring the mechanisms of occurrence and development of Alzheimer’s disease from the perspective of bioinformatics and dynamics will provide guidance for the prognosis,treatment and drug development of Alzheimer’s disease,which is of great significance for improving the survival status of Alzheimer’s patients.The first chapter mainly introduces the basic situation of AD and the research background,significance and current status of miRNA regulation in AD,and gives a brief introduction to the main work in this paper.In the second chapter of this paper,the gene dataset and miRNA dataset are combined to explore the pathogenic pathways related to the occurrence and development of AD,and specifically studies the dual role of p53 in AD based on the bioinformatics method.Firstly,the statistical analysis method is used to identify differentially expressed genes(DEGs)and differentially expressed miRNAs(DEmiRNAs)based on the dataset.GO and KEGG enrichment analysis of DEGs showed that they were mainly involved in synaptic signal transmission and neurotransmitter receptor activity,etc.Then,based on the screened DEGs and DEmiRNAs,a miRNA-gene regulatory network is constructed by integrating different regulatory networks,4 Hub genes and 5 Hub miRNAs were identified from this network.The verification of Hub gene cell expression type showed that they were mainly expressed in neurons.Functional study of Hub miRNA found that miR-4698 was most closely related to p53 signaling pathway.This suggests that miR-4698 and p53 may be involved in the occurrence and development of AD,which is great significance for the study of miR-4698 and p53.In Chapter 3,a p53-Mdm2 dynamic system regulated by miR-4698 with double time delay is proposed based on the analysis results of Chapter 2.Firstly,the stability of the system at the positive equilibrium point is studied theoretically.Secondly,the effect of time delay on the system is discussed by numerical simulation.The results showed that time delay can induce oscillations in the system,and p53 can self-repair,regulate abnormal neuronal death,and regulate the expression of downstream gene GAP43 to regulate abnormal synaptic function,thereby inhibiting the occurrence of AD.Then,the effects of different time delays with miR-4698 in the system were investigated.The results show that the time delay and the self degradation rate k3 of miR-4698,the rate α of p53 promoting the formation of miR-4698,and the inhibition rate d2 of miR-4698 on Mdm2 will be antagonistic,that is,the time delay can induce the oscillation,but the change of the parameter will make the system return to the stable state.Specifically,when k3 is small,time delay T1 induces oscillation,but k3 can suppress the occurrence of oscillation and stabilize the system.α and d2 are completely opposite.In the case of τ1 induced oscillation,as α and d2 increase,the system will return to a stable state.This means that the activation state of p53 can be controlled by controlling parameters such as the degradation rate of miR-4698,which is beneficial for inhibiting the occurrence of AD.In Chapter 4,we summarizes the full text,briefly discusses the innovation and shortcomings of the research methods in this paper,and gives an outlook on future research directions.