The Effect Of CEND1and Its Underlying Mechanism In The Pathogenesis Of Alzheimer’s Disease

Alzheimer disease (AD) is one kind of neurodegenerative diseases, which is characterized by memory loss, congenative disorder gradually and mass mortality of neurons during this process. This disease severly threats the human health. So far, AD can not be cured effectively because of the non-renewable of neurons. Therefore, the researches focusing on the change of earier cell disorders in AD pathogenesis play a significant role in preventing and intervening the neuronal apotosis. According to the current researches, post-mitotic neurons reenter into the cell cycle in AD patents’ brains.However, those neurons start the cell apoptosis pathway rather than dividing, which is termed of Cell Cycle Related Neuronal Death (CRND). While, the cell cycle disorder of neuron is known as the earliest pathology in AD so far. It is very important that the researches concentrating on understanding how the mature neuron is indued to restart the cell cycle process which induces neuronal apoptosis for illustrating the AD pathology. Cyclin Dependent Kinase5(CDK5) is a non-traditonal member of CDKs family. CDK5can suppress the cell cycle process in post-mitotic neurons.CEND1(cell cycle exit and neuronal differentiation1) is identified as a new substrate of CDK5in our lab. It is highly specific expressed in nervous system, which can coordinate the cell division and cell differentiation during the development of nervous system and promote the developmet of neural precursor cell.Normally, CEND1is localized in cytoplasm, however, we found that CEND1is massively accumulated in necleus in AD patients’brains.CEND1is induced to localize to nucleus in neurons treated by A β. According to our further researches, CEND1is shown to be phosphorylated by CDK5at Ser87. The phosphorylation of Ser87impairs the cell cycle depression of CEND1and the effect of CEND1on cell migration. Moreover, the Homo CEND1rather than Mus CEND1is modified by N-glycosylation and the glycosylation promotes the stability of CEND1protein. Nevertheless, the phosphorylation of Ser87decreases the glycosylation level of CEND1. In conclusion, we uncovered that the CDK5can be involved in affecting the CEND1subcellular localization, CEND1protein stability, and glycosylation level through the phosphorylation of CEND1.The phosphorylation of Ser87also influences the function of CENDlin cell proliferation and migration. Because CDK5is abnormally activated in AD, the changes of CEND1function play an important role in AD pathogenesis.