The current treatment of many neurologic disease processes such as Alzheimer~s Disease, Huntington~s Disease, Parkinson~s Disease, multiple sclerosis and stroke is clearly inadequate. A major problem has been that the underlying pathophysiology of these diseases and the underlying biology of the CNS, will the stage be set for the development of more effective treatments. The short-term goal of this project is to develop a better biological understanding of glial cell development. One of the critical issues in CNS development concerns the mechanisms of cellular diversity. The glial O-2A progenitor cell, for example, differentiates into an oligodendrocyte or an astrocyte, depending on the environmental conditions. The intracellular mechanisms that govern this process are unclear. Towards this goal, work has already been initiated on a model system to address glial cell development, the CG-4 glial precursor cell. This cell differentiates into an astrocyte or an oligodendrocyte, depending on the culture conditions. The cell cycle proteins,known to be important in regulating cellular proliferation, are being examined for their role in glial development. Preliminary data already indicate that one of the these proteins, p27kip, may be involved in the mechanism of astrocyte differentiation. Ultimately, we hope to determine the exact mechanisms ofthe cell cycle regulation in glial development, by utilizing biochemical, molecular biological, and cell biological approaches. To delineate the mechanisms by which the cell cycle proteins regulate glial cell development, we propose: 1. To determine the specific cell cycle mechanisms involved in astrocyte differentiation, 2. To determine the specific cell cycle mechanisms involved in oligodendrocyte differentiation, and 3. To identify the physiologic significance of p27 during astrocyte development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08NS001943-01
Application #
2036494
Study Section
NST-2 Subcommittee (NST)
Project Start
1997-01-01
Project End
2001-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065