CELL CYCLE REGULATION AND DIFFERENTIATION

• US 20110085980A1
• Filed: 09/28/2010
• Published: 04/14/2011
• Est. Priority Date: 07/26/2006
• Status: Active Grant

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Barres, Ben A., Dugas, Jason
• Granted Patent: US 7,993,921 B2
• Time in Patent Office: Days
• US Class Current: 424/9.2
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2501/405 Cell cycle regulated proteins, e.g. cyclins, cyclin-dependant kinases
• CPC Class Codes: C12N 2501/60 Transcription factors
• CPC Class Codes: C12N 5/0622 Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells
• CPC Class Codes: G01N 2333/4706 stimulating, promoting or activating activity
• CPC Class Codes: G01N 33/5058 Neurological cells

Abstract

The present invention provides compositions and methods for regulating neural cell proliferation or differentiation. The present invention also provides methods for selecting for bioactive agents effective in regulating proliferation or differentiation.

Claims

1. A method of regulating proliferation or differentiation of a neural cell comprising contacting said neural cell with a bioactive agent effective in modulating the activity or expression level of transcription factor ZFP536, thereby regulating said proliferation or differentiation of said neural cell.

2. The method of claim 1, wherein said neural cell is a glial cell.

3. The method of claim 2, wherein said glial cell has undergone no more than four divisions.

4. The method of claim 2, wherein said glial cell is an immature oligodendrocyte (OL) or an oligodendrocyte precursor cell (OPC).

5. The method of claim 1, wherein said regulation reduces proliferation or promotes differentiation of said neural cell.

6. The method of claim 1, wherein said regulation promotes proliferation or reduces differentiation of said neural cell.

7. The method of claim 1, wherein said bioactive agent is a peptide, protein, peptidomimetic, antibody, aptamer, siRNA, antisense molecule or small organic molecule.

8. A method for screening a candidate bioactive agent effective in regulating proliferation or differentiation of a test neural cell comprising:

(a) contacting said test neural cell with said candidate bioactive agent; and

(b) assaying for a change in the activity or expression level of ZFP536 in said test neural cell as compared to a control neural cell;

wherein a change in the activity or expression level of ZFP536 is indicative of a bioactive agent effective in regulating proliferation or differentiation of said test neural cell.

9. The method of claim 8, wherein said neural cell is a glial cell.

10. The method of claim 9, wherein said glial cell has undergone no more than four divisions.

11. The method of claim 9, wherein said glial cell is an immature oligodendrocyte or an oligodendrocyte precursor cell (OPC).

12. The method of claim 8, wherein said bioactive agent reduces proliferation or promotes differentiation of said neural cell.

13. The method of claim 8, wherein said bioactive agent promotes proliferation or reduces differentiation of said neural cell.

14. The method of claim 8, wherein said bioactive agent is a peptide, protein, peptidomimetic, antibody, aptamer, siRNA, antisense molecule or small organic molecule.

15. A method of assessing the ability of a test neural cell to differentiate comprising:

(a) assaying for an activity or expression level of ZFP536 of said test neural cell; and

(b) comparing said activity or expression level of (a) to that of a control neural cell, wherein a statistically significant increase in activity or expression of ZFP536 implicates the ability of said test neural cell to differentiate.

16. The method of claim 15, wherein said neural cell is a glial cell.

17. The method of claim 16, wherein said glial cell has undergone no more than four divisions.

18. The method of claim 16, wherein said glial cell is an immature oligodendrocyte (OL) or an oligodendrocyte precursor cell (OPC).

19. The method of claim 15, wherein assaying step is performed in vitro.

20. The method of claim 15, wherein assaying step is performed in vivo.