Cell cycle inhibition without disruption of neurogenesis is a strategy for treatment of central nervous system diseases.
Classically, the cell cycle is regarded as the process leading to cellular proliferation. However, increasing evidence over the last decade supports the notion that neuronal cell cycle re-entry results in post-mitotic death. A mature 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 contrast, tumor cells that undergo aberrant cell cycle re-entry divide and can survive. Thus, cell cycle inhibition strategies are of interest in cancer treatment but may also represent an important means of protecting neurons. In this review, we put forth the concept of the "expanded cell cycle" and summarize the cell cycle proteins, signal transduction events and mitogenic molecules that can drive a neuron into the cell cycle in various CNS diseases. We also discuss the pharmacological approaches that interfere with the mitogenic pathways and prevent mature neurons from attempting cell cycle re-entry, protecting them from cell death. Lastly, future attempts at blocking the cell cycle to rescue mature neurons from injury should be designed so as to not block normal neurogenesis.
Liu
Da-Zhi
DZ
Department of Neurology and the M.I.N.D. Institute, University of California at Davis, Sacramento, CA 95817, USA. dzliu@ucdavis.edu
Ander
Bradley P
BP
Sharp
Frank R
FR
D001927:Brain Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D018816:Genes, cdc / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D018797:Cell Cycle Proteins