Claims
- 1. A composition comprising an isolated apoE stable folding intermediate.
- 2. The composition of claim 1, wherein the apoE stable folding intermediate is an apoE4 stable folding intermediate.
- 3. The composition of claim 2, wherein the apoE stable folding intermediate comprises an N-terminal fragment of apoE4.
- 4. The composition of claim 3, wherein the N-terminal fragment of apoE4 is about 22 kDa in size.
- 5. A method of identifying an agent that reduces the lipid binding activity of an apoE stable folding intermediate, the method comprising:
(a) contacting an apoE stable folding intermediate in a solution with a test agent; and (b) determining the effect, if any, of said test agent on the lipid binding activity of the apoE stable folding intermediate.
- 6. The method of claim 5, wherein the solution has a pH in the range of from about 2 to about 6.
- 7. The method of claim 5, wherein the solution has a pH of about 4.0.
- 8. The method of claim 5, wherein solution comprises a denaturant.
- 9. The method of claim 8, wherein the denaturant is urea in a concentration of from about 3 M to about 6 M.
- 10. The method of claim 5, wherein said determining is by turbidimetric analysis of clearing of a lipid-containing vesicle.
- 11. The method of claim 5 wherein the apoE stable folding intermediate is an apoE4 stable folding intermediate.
- 12. A method of identifying an agent that reduces the level of an apoE stable folding intermediate, the method comprising:
(a) contacting an apoE stable folding intermediate in a solution with a test agent; and (b) determining the effect, if any, of said test agent on the level of the apoE stable folding intermediate.
- 13. The method of claim 12, wherein said determining is by far-UV circular dichroism.
- 14. The method of claim 12, wherein said determining is by Fourier transform infrared spectroscopy.
- 15. The method of claim 12, wherein said determining is by dynamic light scattering.
- 16. A method of treating apoE-related disorder, the method comprising administering an effective amount of an agent that reduces the level and/or activity of an apoE stable folding intermediate.
- 17. The method of claim 16, wherein the disorder is a neurological disease.
- 18. The method of claim 16, wherein the neurological disease is Alzheimer's disease.
- 19. The method of claim 18, wherein formation of neurofibrillary tangles are inhibited.
- 20. The method of claim 16, wherein the disorder is a cardiovascular disease.
CROSS-REFERENCE
[0001] This application claims the benefit of U.S. Provisional Patent Application No. 60/402,470 filed Aug. 9, 2002, which application is incorporated herein by reference in its entirety.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH
[0002] This invention was made with government support under grant number RO1NS35939 awarded by the National Institute of Health. The government may have certain rights in this invention.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60402470 |
Aug 2002 |
US |