Name pending approval
Peptide neuroprotection through specific interaction with brain tubulin
Article first published online: 19 JUN 2006
Journal of Neurochemistry
Volume 98, Issue 3, pages 973–984, August 2006
How to Cite
Divinski, I., Holtser-Cochav, M., Vulih-Schultzman, I., Steingart, R. A. and Gozes, I. (2006), Peptide neuroprotection through specific interaction with brain tubulin. Journal of Neurochemistry, 98: 973–984. doi: 10.1111/j.1471-4159.2006.03936.x
- Issue published online: 19 JUN 2006
- Article first published online: 19 JUN 2006
- Received March 16, 2006; revised manuscript received April 2, 2006; accepted April 4, 2006.
- activity-dependent neuroprotective protein;
This study aimed to identify the neuronal target for the potent neuroprotective peptide NAP. When added to pheochromocytoma cells (neuronal model), NAP was found in the intracellular milieu and was co-localized with microtubules. NAP induced neurite outgrowth and protected primary neurons against microtubule-associated ZnCl2 toxicity. Rapid microtubule reorganization into distinct microtubules ensued after NAP addition to both pheochromocytoma cells and primary cerebral cortical neurons, but not to fibrobalsts. While binding neuronal tubulin and protecting pheochromocytoma cells against oxidative stress, NAP did not bind tubulin extracted from fibroblasts, nor did it protect those cells against oxidative stress. Affinity chromatography identified the brain-specific βIII-tubulin as a major NAP binding protein. Paclitaxel (a microtubule aggregating agent that interacts with β-tubulin) reduced NAP tubulin binding. Thus, the underlying mechanism for the neuroprotection offered by NAP is targeting neuronal microtubules that are essential for neuronal survival and function.