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CELL CYCLE REGULATION IN THE POST-MITOTIC NEURONAL CELLS

Wang, Li
http://rave.ohiolink.edu/etdc/view?acc_num=case1184254319

Abstract Details

2007, Doctor of Philosophy, Case Western Reserve University, Genetics.
A normal cell cycle is essential for cell proliferation in embryonic development. Once the appropriate numbers of cells are generated, however, there are various populations, e.g. neurons, which will exit permanently from the cell cycle in order to undergo differentiation. It has been widely believed that mature CNS neurons are regarded as permanently post-mitotic and unable to reenter cell cycle. However, emerging data suggests that in different neurodegenerative disease and their mouse models there is a significant deregulation of cell cycle control in specific neuronal populations in precisely those regions where cell is lost.It seems that the neurons must constantly hold the cell cycle in check after their differentiation. This raises the important but often ignored question: how do adult neurons regulate their cell cycle machinery? Our studies indicate the certain molecules might take on an apparently different role in neurons than they do in other types of cells. In Chapter 2, I report on the role of E2F1 in cell cycle regulation of adult neurons. E2F1 has been described as an important cell cycle initiator because of its ability to positively regulate the transcription of genes that are important for normal cell cycle progression. As part of my thesis work, I have found that, in adult neurons, E2F1 plays a role as a cell cycle suppressor. In Chapter 3, I report on my analysis of a unique cyclin dependent kinase, CDK5, in neuronal cell cycle regulation. Following up on previous work showing that CDK5 is important in suppressing cell cycle progression in post-mitotic neurons, we have further shown that it is the nuclear localization of CDK5 that is important for holding the cell cycle in check in post-mitotic neurons stressed by Aâ.Overall, our findings indicate that it is crucial for post-mitotic neurons to hold their cell cycle in check. Both E2F1 and CDK5 apparently play central roles in this process. The investigation of those signaling pathways in the future has the potential not only to improve our understanding of the basic biology of neuronal degenerative diseases, but also offer new pathways to plan for therapeutic interventions.
Karl Herrup (Advisor)
Cell cycle regulation; E2F1; Cdk5

Recommended Citations

Citations

  • Wang, L. (2007). CELL CYCLE REGULATION IN THE POST-MITOTIC NEURONAL CELLS [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1184254319

    APA Style (7th edition)

  • Wang, Li. CELL CYCLE REGULATION IN THE POST-MITOTIC NEURONAL CELLS. 2007. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1184254319.

    MLA Style (8th edition)

  • Wang, Li. "CELL CYCLE REGULATION IN THE POST-MITOTIC NEURONAL CELLS." Doctoral dissertation, Case Western Reserve University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1184254319

    Chicago Manual of Style (17th edition)

case1184254319
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© 2007, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.