Document Detail


Cell cycle inhibition without disruption of neurogenesis is a strategy for treatment of central nervous system diseases.
MedLine Citation:
PMID:  19944161     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Da-Zhi Liu; Bradley P Ander; Frank R Sharp
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2009-11-24
Journal Detail:
Title:  Neurobiology of disease     Volume:  37     ISSN:  1095-953X     ISO Abbreviation:  Neurobiol. Dis.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-17     Completed Date:  2010-06-08     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  9500169     Medline TA:  Neurobiol Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  549-57     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Inc.
Affiliation:
Department of Neurology and the M.I.N.D. Institute, University of California at Davis, Sacramento, CA 95817, USA. dzliu@ucdavis.edu
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Brain Diseases / drug therapy,  metabolism,  physiopathology*
Cell Cycle / drug effects,  physiology*
Cell Cycle Proteins / drug effects,  genetics,  metabolism
Cell Death / drug effects,  physiology
Drug Evaluation, Preclinical / methods
Genes, cdc / drug effects,  physiology
Humans
Nerve Degeneration / drug therapy,  metabolism,  physiopathology*
Neurogenesis / drug effects,  physiology
Signal Transduction / drug effects,  physiology
Grant Support
ID/Acronym/Agency:
NS054652/NS/NINDS NIH HHS; R01 NS054652-01A1/NS/NINDS NIH HHS; R01 NS054652-02/NS/NINDS NIH HHS; R01 NS054652-03/NS/NINDS NIH HHS; R01 NS054652-04/NS/NINDS NIH HHS; R01 NS054652-05/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Lyophilization monophase solution technique for improvement of the physicochemical properties of an ...
Next Document:  Inhibition of anticancer drug efflux transporter P-glycoprotein by rosemary phytochemicals.