The first two authors contributed equally to this work.
Novel lipoxygenase inhibitors as neuroprotective reagents
Article first published online: 25 OCT 2007
Copyright © 2007 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 86, Issue 4, pages 904–909, March 2008
How to Cite
van Leyen, K., Arai, K., Jin, G., Kenyon, V., Gerstner, B., Rosenberg, P. A., Holman, T. R. and Lo, E. H. (2008), Novel lipoxygenase inhibitors as neuroprotective reagents. J. Neurosci. Res., 86: 904–909. doi: 10.1002/jnr.21543
- Issue published online: 11 FEB 2008
- Article first published online: 25 OCT 2007
- Manuscript Accepted: 8 AUG 2007
- Manuscript Revised: 3 AUG 2007
- Manuscript Received: 11 JUN 2007
- NIH. Grant Numbers: NS049430, GM56062, NS38475
- American Heart Association. Grant Number: 0530283N
- Alzheimer's disease;
- Parkinson's disease;
- oxidative stress;
- drug screening;
The lipid-metabolizing enzyme 12/15-lipoxygenase (12/15-LOX) mediates cell death resulting from oxidative stress in both neurons and oligodendrocytes. Specifically, it may contribute to the pathophysiology of stroke and Alzheimer's and Parkinson's diseases. We report here that two of three specific 12/15-LOX inhibitors, derived from a virtual screen by computer modeling and validated by inhibition of recombinant human 15-LOX in vitro, are able to rescue both neuronal as well as oligodendroglial cells from cell death induced by oxidative stress. Thus, in a fairly streamlined process, an initial virtual screen of 50,000 compounds in a library of drug-like molecules has led to the identification of two novel drug candidates for targeting LOX. Future studies of these novel neuroprotective inhibitors of 12/15-LOX may provide new therapeutic opportunities to combat stroke and other neurodegenerative diseases. © 2007 Wiley-Liss, Inc.