The Investigation Of Neuronal Specific Protein CEND1 In The Pathogenesis Of AD

Alzheimer's disease(AD)is a neurodegenerative disease characterized by progressive memory impairment and cognitive dysfunction,often accompanied by a series of neuropsychiatric symptoms.Irreversible neuron death is the direct cause of AD disease.There is no cure for AD.Therefore,the study of the pathogenesis of AD is of great significance for the prevention and treatment of AD.The study found that neurons in the later stages of the process of AD disease reentered the cell cycle,but these neurons did not perform normal mitosis but eventually died.Cell cycle disorders are the early changes in the cellular functions of the known AD pathogenesis,as early as neurofibrillary tangles and amyloid plaques.Cyclin Dependent Kinase 5(CDK5)is an important member of the CDK family.It plays an important role in regulating nerve fiber entanglement and cell cycle progression,so it is closely related to the pathogenesis of AD.CDK5 is a protein kinase,which helps to better understand the role of CDK5 in the pathogenesis of AD by identifying and studying its downstream substrate.In the early stage of our laboratory,a protein spectrum identification method was found in the sample of AD patients.Cell cycle exit and neuronal differentiation 1(CEND1)are the new fifth of CDK5,which is closely associated with AD disease.We found that CEND1 is a specific expression of mitochondrial protein in neurons,and CEND1 is also distributed in the synapse,mainly in front of the synapse.CEND1 localization suggests that CEND1 may regulate mitochondrial function before the synapses.We then found that CDK5 phosphorylated CEND1 in the 10th position of serine,and could significantly induce the degradation of CEND1.In the cell model and animal model of AD,we detected a significant decrease in CEND1 protein expression level,and accompanied with neuronal mitochondrial function and cell cycle disorder.Taken together,our findings and proves that CDK5 through regulating CEND1 phosphorylation and protein stability,affect neuronal mitochondrial function and cell cycle in neurons,may be in the AD of the early lesion plays an important role.This study provides a new drug development target for the prevention and treatment of AD.