Late Phase Cell-Cycle Proteins in Postmitotic Neurons: Relation to Alzheimer’s Disease?

Cell cycle re-entry has become a well established model of neuropathogenesis in Alzheimer’s disease (AD). We and others have demonstrated expression of early phase cell cycle-related proteins in the vulnerable neurons in AD. Evidence that this represents a bona fide mitotic event is verified by the observation that DNA replication does in fact occur in these cells. Notably, the relatively early occurrence of cell cycle events in AD suggests that a mitotic cell cycle related mechanism may play a pivotal role in the disease. Still, a number of features of the cell cycle re-entry phenotype have remained elusive to the role of ectopic protein expression in the process of neuronal cell death. Late phase cell cycle proteins regulate separation and segregation of chromosomes. The centromere region is crucial to this process. Until recently there has been no data on the role of proteins controlling the centromere region in postmitotic neurons. This new data suggests that cohesin complexes that mediate sister?chromatid cohesion in dividing cells may also contribute to gene regulation in postmitotic cells. Therefore, centromere-cohesin proteins may play a secondary role in the cell, i.e. one that is independent of their role in cohesion and chromosome segregation. Evidence demonstrating that instability of centromere-cohesion dynamics in the early phases of the cell cycle which coincide with re-entry alteration of cortical neurons enables the possibility to further elucidate initial processes leading to AD.