NGF/P75 in cell cycle and tetraploidy

Abstract

Neurotoxicity, neurodegeneration, and other disorders affecting neuron survival are often related to cell cycle reentry in neurons. Traditionally, cell cycle reentry of these postmitotic cells has been thought to be associated with apoptosis. Nevertheless, cell cycle reentry and DNA synthesis in neurons could also lead to tetraploidy which may explain long-lasting neurodegenerative processes. During development, a subpopulation of newborn neurons reactivates the cell cycle and becomes tetraploid in response to p75NTR activation. These neurons enlarge their cell bodies and increase their dendritic trees, thus generating specific neuronal populations that innervate particular areas. Pathological states in the nervous system could also lead to p75NTR-dependent neuronal tetraploidy. De novo tetraploid neurons might become structurally and functionally altered, thus leading to neurodegeneration at late stages of the disease. This chapter describes what is currently known about the interplay between p75NTR and the cell cycle, stressing the role played by different p75NTR interactors, including the MAGE and Bex1/NADE adaptor proteins and the transcription factors SC1, NRIF, and Sall2, in cell cycle regulation. The chapter also discusses on the effects of p75NTR, as a cell cycle regulator, in neural stem cell proliferation, neurogenesis, and neuronal tetraploidization, as well as on the connection of p75NTR in pathology, including its putative effects in neurodegeneration.