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Chin. Med. J. 2009, 122, 1666 1673. 226. Kimura, Y, Taniguchi, M, Baba, Phloridzin K. Antitumor and antimetastatic effects on liver of triterpenoid fractions of Ganoderma lucidum: mechanism of action and isolation of an active substance. Anticancer Res. 2002, 22, 3309 3318.© 2010 by the authors, licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license. Cell cycle inhibition as a strategy for treatment of central nervous system diseases which must not block normal neurogenesis Da Zhi Liu, Bradley P. Ander, and Frank R. Sharp Department of Neurology and the M.I.N.D. Institute, University of California at Davis, Sacramento, California 95817 Abstract Classically, the cell cycle is regarded as the central 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. Keywords neuron, cell cycle, mitogen, mitogenic pathway, cell cycle re entry, cell stress, CNS diseases, neurogenesis Introduction Postmortem studies over the last decade have revealed pathological evidence of aberrant expression of cell cycle related molecules in the neurons of the hippocampus, subiculum, locus coeruleus and dorsal raphe nuclei.
Direct proof of DNA replication was also identified in brains of patients with Alzheimer,s disease , epilepsy, Parkinson,s disease and amyotrophic lateral sclerosis . These important discoveries stimulated new hypotheses and studies challenging the traditional concept that post mitotic neurons are terminally differentiated and maintained in the G0 quiescent phase. Although still controversial, evidence Corresponding author: Dr. Da Zhi Liu, Department of Neurology and the M.I.N.D. Institute, University of California at Davis Medical Center, 2805 50th St