Premium
Peptide neuroprotection through specific interaction with brain tubulin
Author(s) -
Divinski Inna,
HoltserCochav Miri,
VulihSchultzman Inna,
Steingart Ruth A.,
Gozes Illana
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03936.x
Subject(s) - nap , neuroprotection , tubulin , microtubule , neurite , microbiology and biotechnology , paclitaxel , chemistry , biology , biochemistry , in vitro , neuroscience , genetics , chemotherapy
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 ZnCl 2 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.