Claims
- 1. A transgenic mouse comprising:
a transgenic nucleotide sequence, integrated into the genome of said mouse, encoding human α-synuclein operably linked to a promoter; wherein the transgenic nucleotide sequences are expressed, and wherein, as a result of said expression, said transgenic mouse develops intraneuronal inclusions associated with neurodegenerative disease.
- 2. The transgenic mouse of claim 1, wherein said promoter comprises platelet-derived growth factor β (PDGF-β) promoter.
- 3. The transgenic mouse of claim 2, wherein a SV40 derived intron operably links said platelet-derived growth factor β (PDGF-β) promoter with said transgenic nucleotide sequence.
- 4. The transgenic mouse of claim 1, wherein the transgenic nucleotide sequence encoding human α-synuclein is overexpressed as compared to a non-transgenic mouse of the same strain.
- 5. A method of screening for therapeutic agents that inhibit amyloidogenesis and amyloid deposition associated with neurodegenerative disease and α-synuclein aggregation, comprising:
administering a candidate therapeutic agent to a transgenic mouse, comprising a transgenic nucleotide sequence encoding human α-synuclein operably linked to a promoter, wherein the transgenic nucleotide sequence is expressed, and wherein, as a result of said expression, said transgenic mouse develops, intracellular inclusions associated with neurodegenerative disease; and evaluating the effect of said therapeutic agent upon neurophysiological characteristics, associated with said neurodegenerative disease.
- 6. The method of claim 5, wherein the neurophysiological characteristics associated with neurodegenerative disease are α-synuclein aggregation in neurons resulting in neuronal inclusions and motor deficits.
- 7. A method of screening for therapeutic agents that inhibit intraneuronal inclusion formation and aggregate formation associated with neurodegenerative disease and α-synuclein aggregation, comprising:
generating a first stable cell line overexpressing α-synuclein; generating a second stable cell line overexpressing β-synuclein; contacting with said first and second stable cell lines a candidate agent; and evaluating the effect of said candidate on intraneuronal inclusion formation within said first and second stable cell lines respectively.
- 8. The method of screening of claim 7, wherein said cell line is GT1-7.
- 9. The method of screening of claim 7, wherein said cell line is B103.
- 10. A method to modulate production of α-synuclein aggregates in a subject comprising administering an effective amount of inhibitor of α-synuclein aggregation and reducing α-synuclein aggregation.
- 11. The method of claim 10, wherein the inhibitor of α-synuclein aggregation comprises β-synuclein or a derivative thereof.
- 12. The method of claim 11, wherein the inhibitor comprises a nucleic acid.
- 13. The method of claim 12, wherein the nucleic acid is functionally linked to regulatory elements for expression in a cell.
- 14. The method of claim 12, wherein the nucleic acid is modified.
- 15. The method of claim 10, wherein the inhibitor comprises a peptide or protein.
- 16. The method of claim 15, wherein the protein or peptide is modified.
Parent Case Info
[0001] This application claims the benefit of priority of U.S. Provisional Application Ser. No. 60/183,571 to Eliezer Masliah et al., filed Feb. 18, 2000 and entitled “METHOD FOR SCREENING FOR ANTI-AMYLOIDOGENIC PROPERTIES AND METHOD FOR TREATMENT OF NEURODEGENERATIVE DISEASE”, the entire contents of which is incorporated herein by reference.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/US01/05569 |
2/20/2001 |
WO |
|