Using Primate Models To Explore The Early Onset Characteristics And Mechanisms Of Parkinson's Disease

Parkinson disease is the second largest neurodegenerative disease in the world after Alzheimer disease(AD).Most patients with Parkinson’s disease in the late onset with significant behavioral manifestations,for the early Parkinson’s disease patients lack effective prevention and diagnostic methods.A lot of progress has been made in the study of Parkinson’s disease,and many genes related to Parkinson’s disease are found,include a-synuclein,PARK2(parkin)and PARK6(PINK1).The early molecular biology characteristics and performance of Parkinson’s disease for the diagnosis and pathogenesis of the study is very important.Disease animal models,including chemical induction models and transgenic animal models,play a very important role in the study of human diseases.The transgenic animal model can help researchers to study the entire pathogenesis of the diseases,especially for some diseases that at the early onset of the disease did not owned significantly manifest.And the clinical method is difficult to diagnose the disease,such as the previously mentioned Parkinson’s disease and Alzheimer’s disease.Therefore,for Parkinson’s disease,animal models of disease,especially genetically engineered animal models based on genetic engineering,are very important to the study of Parkinson’s disease.Based on the research and analysis of Parkinson’s disease-related genes,the laboratory constructs transgenic animal model and genetically modified animal model by means of genetic engineering technology by means of laboratory assisted reproductive technology platform.The animal model of a-synuclein overexpressing was established by lentiviral vector.The animal model of PARK2 and PARK6 gene knockout was further constructed by CRISPR/cas9 technique.Animals were used to analyze the differences in gene expression and abnormal expression of small RNA in animal blood.By means of the laboratory model of Parkinson’s disease(A53T Rhesus monkey and CRISPR/cas9 modified cynomolgus monkeys)combined with transcriptome sequencing and small RNA sequencing method.With this method to explore the early pathogenesis of Parkinson’s disease.At the same time with the second generation sequencing technology to calculate CRISPR/cas9 sg-RNA efficiency analysis.The results showed that there were significant differences in gene expression between the experimental group and the control group.The main protein coding genes mainly involved hemoglobin oxygen transfer,ribosome subunit,mitochondria and major histocompatibility complex(MHC).The data of the transcriptome were analyzed by WGCNA,and the results showed that the functions of expressed genes were membrane,recognition and antigen transfer.In addition,the experimental group and control group of experimental animal blood biochemical indicators analysis,early research for Parkinson’s disease is also very important,blood biochemical analysis showed that there are multiple indicators between experimental group values and control group values were significantly different,Suggesting that Parkinson’s disease may be at the early onset presence of abnormal immune function,some indicators have been found in the study and the incidence of Parkinson’s disease patients.Once again it was demonstrated that laboratory-built animal models can help and apply to the study of Parkinson’s disease.From the analysis results of the transcriptome data,there was a difference in the immune function between the experimental group and the control group,which was very important for understanding and studying the early pathogenesis of Parkinson’s disease.It is suggested that this may provide a new research direction and ideas for the early diagnosis of Parkinson’s disease from the aspects of immune dysfunction.For the analysis of small RNA,miR-144-3P and miR-144-5P were found to be significantly differentially expressed in some experimental animals.The function of miR-144-was mainly related to the tumor.According to the actual animal case,the predicted regulatory genes for miR-144 include PINK1,PARK2 and alpha-synuclein,all of these genes were associated with Parkinson’s disease.In addition,the latest study found that abnormal expression of miR-144 was detected on the corpse of patients who had been diagnosed with Parkinson’s disease,in which the target genes predicted in the article included the predicted target genes in laboratory analysis.Through the PCA analysis of the experimental samples,it was found that the experimental group and the control group could be distinguished according to the expression of miR-144.Because of the experimental animals were constructed using chemical techniques and the age of the experimental animals was still relatively small,the animals in the experimental group had not yet exhibited typical Parkinson’s behavioral manifestations.These experimental animals provide an opportunity to help us participate the early studies of Parkinson’s disease,so we can carry out the necessary molecular biology tests on these animals in the future,and use the medical image observation means to track the animals,may be we can capture of some of the more significant molecular biology characteristics and performance in the molecular biology level.And this can help diagnosis and detection of Parkinson’s disease in the future at the early time.The gene modification efficiency of embryonic sg-RNA was analyzed by using sequencing analysis of PCR products,this provide an important reference for the next step in constructing transgenic nonhuman primate animal model.Using the animal model of disease combined with the current sequencing technology and bioinformatics analysis means,it is of great significance to explore the early pathogenesis and mechanism of human disease.Combined with experimental research in the relationship between immune dysfunction and Parkinson’s disease,maybe can better simulate the actual situation of Parkinson’s disease.These new design ideas can help improve the construction and use of these animal models,it maybe can better simulate the real pathogenesis of Parkinson’s disease.Especially for Parkinson’s disease and Alzheimer’s disease,these can do much help to human disease research and provide important guidance and references.