Department of Molecular, The Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106-9610, USA.
J Alzheimers Dis. 2010;19(4):1377-86. doi: 10.3233/JAD-2010-1335.
NAP (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln) is a neuroprotective peptide that shows cognitive protection in patients with amnestic mild cognitive impairment, a precursor to Alzheimer's disease. NAP exhibits potent neuroprotective properties in several in vivo and cellular models of neural injury. While NAP has been found in many studies to affect microtubule assembly and/or stability in neuronal and glial cells at fM concentrations, it has remained unclear whether NAP acts directly or indirectly on tubulin or microtubules. We analyzed the effects of NAP (1 fM-1 microM) on the assembly of reconstituted bovine brain microtubules in vitro and found that it did not significantly (p< 0.05) alter polymerization of either purified tubulin or of a mixture of tubulin and unfractionated microtubule-associated proteins. NAP also had no significant effect (p < 0.05) on the growing and shortening dynamics of steady-state microtubules at their plus ends, nor did it alter the polymerization or dynamics of microtubules assembled in the presence of 3-repeat or 4-repeat tau. Thus, the neuroprotective activity of NAP does not appear to involve a direct action on the polymerization or dynamics of purified tubulin or microtubules.
NAP（天冬酰胺-丙氨酸-脯氨酸-缬氨酸-丝氨酸-异亮氨酸-脯氨酸-谷氨酰胺）是一种具有神经保护作用的肽，在遗忘型轻度认知障碍患者（阿尔茨海默病的前驱期）中具有认知保护作用。NAP 在几种体内和细胞神经损伤模型中均表现出强大的神经保护作用。虽然在许多研究中发现 NAP 在 fM 浓度下影响神经元和神经胶质细胞中的微管组装和/或稳定性，但尚不清楚 NAP 是否直接或间接作用于微管蛋白或微管。我们分析了 NAP（1 fM-1 microM）对体外重组牛脑微管组装的影响，发现它对纯化微管蛋白或微管蛋白和未分级微管相关蛋白混合物的聚合均无显著影响（p<0.05）。NAP 对稳态微管末端的生长和缩短动力学也没有显著影响（p<0.05），也不会改变 3 重复或 4 重复 tau 存在下组装的微管的聚合或动力学。因此，NAP 的神经保护活性似乎不涉及对纯化微管蛋白或微管的聚合或动力学的直接作用。
