p27, The Cell Cycle and Alzheimer´s Disease.

The cell cycle consists of successive events that lead to the generation of new cells. The cell cycle is regulated by different cyclins, cyclin-dependent kinases (CDKs) and their inhibitors, such as p27Kip1. At the nuclear level, p27Kip1 has the ability to control the evolution of different phases of the cell cycle and oppose cell cycle progression by binding to CDKs. In the cytoplasm, diverse functions have been described for p27Kip1, including microtubule remodeling, axonal transport and phagocytosis. In Alzheimer's disease (AD), alterations to cycle events and a purported increase in neurogenesis have been described in the early disease process before significant pathological changes could be detected. However, most neurons cannot progress to complete their cell division and undergo apoptotic cell death. Increased levels of both the p27Kip1 levels and phosphorylation status have been described in AD. Increased levels of Aß42, tau hyperphosphorylation or even altered insulin signals could lead to alterations in p27Kip1 post-transcriptional modifications, causing a disbalance between the levels and functions of p27Kip1 in the cytoplasm and nucleus, thus inducing an aberrant cell cycle re-entry and alteration of extra cell cycle functions. Further studies are needed to completely understand the role of p27Kip1 in AD and the therapeutic opportunities associated with the modulation of this target.