Neuroscience 2001 Abstract
| Presentation Number: | 859.16 |
|---|---|
| Abstract Title: | Identification of agents that selectively decrease Aβ42 secretion from cultured cells without affecting APP or Notch processing. |
| Authors: |
Weggen, S.*1
; Pietrzik, C. U.1
; Sagi, S. A.1
; Eriksen, J.2
; Murphy, M. P.2
; Golde, T. E.2
; Koo, E. H.1
1Neurosciences, UCSD, La Jolla, CA 2Pharmacology, Mayo Clinic Jacksonville, Jacksonville, CA |
| 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 4:00 PM-5:00 PM |
| Location: | Exhibit Hall VV-30 |
| Keywords: | AMYLOID PRECURSOR PROTEIN, ALZHEIMER, AMYLOID |
Pharmacological agents that selectively inhibit production of the highly amyloidogenic Aβ42 peptide and do not interfere with other physiological functions of γ-secretase may have superior features for the treatment of Alzheimer’s disease (AD). Here we report the identification of a class of compounds that selectively decreased the secretion of Aβ42 from a variety of cultured cells of both neural and non-neural origin through a novel mechanism. The reduction in Aβ42 levels ranged from 30 to 70% without significant changes in total Aβ levels, especially Aβ40 species. Moreover, short-term administration in APP-transgenic mice lowered brain Aβ42 levels (Eriksen, J. et. al., SFN abstract, 2001). In contrast to published γ-secretase inhibitors, these compounds did not significantly perturb APP or notch processing. In particular, the reduction in Aβ42 levels was not accompanied by an increase in APP C-terminal fragments, nor any changes in APPs secretion, APP internalization, or APP turnover. Significantly, transmembrane cleavage of the Notch-1 was not impaired. The accompanying abstract (Sagi, S. et. al.) provides further characterization of the changes in Aβ peptides following drug treatment. These compounds may therefore provide an excellent basis for extended compound screenings and chemical modifications approaches which could lead to the development of improved AD drugs that target production of Aβ42, the putative pathogenic isoform of Aβ.
Supported by NIH AG12376
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2001 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2001. Online.
Copyright © 2001-2026 Society for Neuroscience; all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
