Neuroscience 2001 Abstract
| Presentation Number: | 859.15 |
|---|---|
| Abstract Title: | Agents that selectively decrease Aβ42 levels from cultured cells paradoxically increase Aβ38 levels. |
| Authors: |
Sagi, S. A.*1
; Weggen, S.1
; Wang, R.3
; Golde, T. E.2
; Koo, E. H.1
1Dept Neurosci, UCSD, La Jolla, CA 2Dept Pharmacology, Mayo Clinic Jacksonville, Jacksonville, FL 3Dept Human Genetics, Mount Sinai School of Medicine, New York, NY |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Neurodegenerative Disorders -- Alzheimers Disease: APP, presenilin and secretases |
| Session: |
859. Neurodegenerative disorders: Alzheimer's disease--APP processing and function V Poster |
| Presentation Time: | Wednesday, November 14, 2001 3:00 PM-4:00 PM |
| Location: | Exhibit Hall VV-30 |
| Keywords: | BETA AMYLOID, ALZHEIMER, AMYLOID PRECURSOR PROTEIN |
The identification of compounds that selectively reduce the amount of amyloidogenic Aβ42 peptide may provide the basis for the development of pharmacological treatments for Alzheimer's disease. In the accompanying posters (Eriksen, J. et. al., and Weggen, S. et. al., SFN abstracts, 2001), we described agents that selectively reduce the levels of Aβ42 in medium from a variety of cell lines and from brains of APP transgenic mice. To understand the action of this class of compounds, we investigated their effect on various Aβ species by performing MALDI-TOF and bicine-urea gel analyses on conditioned medium from cells cultured with these compounds. Surprisingly, we found that the selective reduction in Aβ42 is accompanied by an increase in Aβ38, while levels of Aβ40 as well as other shorter Aβ peptides (Aβ34, Aβ37, and Aβ39) remained relatively constant. We are currently investigating if this shift can be induced in vivo and if other agents have similar activity. To our knowledge this is the first time chemical intervention has shifted Aβ species, rather than decreased overall Aβ peptides. This shift suggests that these compounds act by a novel mechanism. These findings are particularly interesting in light of the absence of any effects of these compounds on APP or Notch processing. Further, our results suggest that agents less toxic than non-selective γ-secretase inhibitors exist and may be optimized for AD therapeutics.
Supported by supported in part by NIH AG12376
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2001 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2001. Online.
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