Neuroscience 2000 Abstract
| Presentation Number: | 299.3 |
|---|---|
| Abstract Title: | Isolation and testing of the amyloid-inhibiting ingredients derived from the natural beta-amyloid protein fibrillogenesis inhibitor PTI-00703;<SUP>tm<SUP>. |
| Authors: |
Snow, A. D.*1
; Choi, P. Y-.1
; Cummings, J. A.1
; Wood, S.2
; Kirschner, D. A.3
; Castillo, G. M-.1
1ProteoTech Inc., Kirkland, WA 2Chemistry, Brigham Young University, Salt Lake City, UT 3Cell Biology, Boston College, Boston, MA |
| Primary Theme and Topics |
J. Disorders of the Nervous System and Aging - 126. Degenerative disease: Alzheimer's-beta amyloid |
| Secondary Theme and Topics | J. Disorders of the Nervous System and Aging<br />- 130. Degenerative disease: Alzheimer's-other |
| Session: |
299. Degenerative disease: Alzheimer's--beta amyloid: aggregation and inflammation Slide |
| Presentation Time: | Monday, November 6, 2000 1:30 PM-1:45 PM |
| Location: | Room 268 |
| Keywords: | Alzheimer's disease, therapeutics, PTI-00703, PTI-777 |
PTI-00703TM (703) is a derivative from the Amazon rain forest woody vine, Uncaria tomentosa (Cat's claw) previously discovered by our group to inhibit the formation, deposition and growth of Alzheimer's beta-amyloid protein (Aβ) deposits. In the present study assay guided fractionation and HPLC were used to isolate, characterize and test water-soluble active ingredients within 703 that possess potent Aβ fibrillogenesis inhibitory activity. Up to 7 major water-soluble ingredients (collectively known as PTI-777) were purified and tested in various assays to determine their efficacy in comparison to 703 and to major alkaloids present in Cat's claw. Thioflavin T fluorometry, Congo red staining and electron microscopy data demonstrate that PTI-777 is a more potent inhibitor of Aβ fibrillogenesis than 703 alone. In one study, incubation of 703 with Aβ 1-42 for 1 day (1:1 weight ratio) caused a 53.2% disruption of Aβ fibrils, whereas PTI-777 resulted in a significant 87.3% inhibiton. In a rodent model 1 week co-infusion of 703 + Aβ 1-42 into hippocampus led to a 51.0% inhibition of Aβ fibril depostion into brain, whereas PTI-777 + Aβ 1-42 resulted in a significant 89.2% inhibition. Amyloid inhibitory effects were not observed using purified alkaloids derived from Cat's claw indicating that PTI-777 likely consists of unique non-alkaloid products. Identification, characterization and further testing of PTI-777 will lead to the development of a natural Aβ fibrillogenesis inhibitor as a future pharmaceutical.
Supported by NIH SBIR Award and ProteoTech Inc
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2000 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2000. Online.
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