WITHDRAWN: Cell cycle Inhibition as a Strategy for Treatment of Central Nervous System Diseases

Ahead of Print article withdrawn by publisher. Classically, the cell cycle is regarded as the central process leading to cellular proliferation. However, increasing evidence has substantiated the concept that cell cycle re-entry by neurons leads to post-mitotic death. A neuron that re-enters the cell cycle can neither advance to a new G0 quiescent state nor revert to its earlier G0 state. This presents a critical dilemma to the neuron from which death may be an unavoidable, but necessary, outcome for adult neurons attempting to complete the cell cycle. In this review we summarize the signal transduction events and mitogenic molecules that can drive the neuron into the cell cycle in various CNS diseases, and discuss the hypthesis that two main requirements are to be met for neuronal cell cycle re-entry: (1) an elevation in cell cycle proteins and (2) increased pro-mitogenic signals. Pharmacological approaches and patents are outlined that interfere with the mitogenic pathways, prevent mature neurons from attempted cell cycle re-entry, and protect them from cell death.