Neuroscience 2001 Abstract
| Presentation Number: | 496.6 |
|---|---|
| Abstract Title: | THE NEUROPROTECTIVE CANNABINOID-DERIVATIVE DEXANABINOL IS AN INHIBITOR OF NF-κB. |
| Authors: |
Juettler, E.*1
; Fink, G.2
; Prinz, S.1
; Schwaninger, M.1
1Department of Neurology, University of Heidelberg, Heidelberg 69120, Germany 2Pharmos Ltd., Kiryat Weizman, Rehovot 76326, Israel |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Intracellular Signalling Pathways -- Transcriptional regulation |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- Glia<br />-- Other |
| Session: |
496. Intracellular signaling pathways: transcriptional regulation--life or death decisions Poster |
| Presentation Time: | Tuesday, November 13, 2001 9:00 AM-10:00 AM |
| Location: | Exhibit Hall F-58 |
| Keywords: | NUCLEAR FACTOR KAPPA B, CANNABINOIDS, DEXANABINOL, NEUROPROTECTION |
Dexanabinol is a derivative of the cannabinoid tetrahydrocannabinol (THC). Dexanabinol shares the neuroprotective properties of THC but lacks its psychotropic effects. Several studies have shown anti-inflammatory effects of dexanabinol including inhibition of tumor necrosis factor (TNF)-α expression. The expression of TNF-α and various other mediators of inflammation is regulated by transcription factor NF-κB. NF-κB, an essential transcription factor for many genes, is involved in the pathophysiology of brain damage and is a major regulator of neural cell death. To investigate the effect of dexanabinol on NF-κB activation we have transiently transfected U373 MG cells with a reporter fusion gene under transcriptional control of NF-κB. Stimulation of NF-κB activity by TNFα detected by luciferse assay was inhibited by dexanabinol in a concentration-dependent manner. Activation of NF-κB is known to be due to the degradation of the inhibitor IκBα. Dexanabinol inhibited the TNF-α-induced degradation of IκBα as shown by Western Blot analysis. Furthermore we were able to show by gelshift assay that, as a consequence, dexanabinol reduced the activation and nuclear translocation of NF-κB. In summary, we show that dexanabinol is capable of inhibiting the activation of NF-κB by reducing degradation of IκBα. Thereby, Dexanabinol could protect neural cells during inflammation or ischemia.
*Department of Neurology, University of Heidelberg, Germany
+ Pharmos Ltd., Israel.
*Department of Neurology, University of Heidelberg, Germany
+ Pharmos Ltd., Israel.
Supported by Pharmos Ltd.
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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