又有惊喜!阿司匹林或能治疗老年痴呆等神经退行性疾病
2015/12/03
11月25日发表于《PLOS One》杂志上的研究揭示,阿司匹林和水杨酸衍生物可帮助对抗许多神经退行性疾病。


11月25日发表于《PLOS One》杂志上的研究揭示,阿司匹林和水杨酸衍生物可帮助对抗许多神经退行性疾病。

自古以来,植物用于治疗已十分常见。在过去20年里,FDA批准的天然药物或天然产物的衍生物药品主要来源均为植物。水杨酸及其衍生物就是一个典型的例子,水杨酸是乙酰水杨酸和阿司匹林的主要分解产物,也是调控植物免疫系统的关键激素。水杨酸及其衍生物被用于治疗疼痛、发烧和炎症已有数千年。目前美国每天消耗八千万片阿司匹林,主要用于治疗心脏病发作、中风和某些癌症。

本研究资深作者康奈尔大学汤普森研究所Daniel Klessig教授专注于水杨酸的研究已有很多年,主要目标为植物。水杨酸对一些植物的影响已有研究证实,然而这些影响机制在人体的效应与植物等同。

阿司匹林可作用于阿尔兹海默症和帕金森氏症?

如今看来,水杨酸令人印象深刻之处可能要扩张至老年痴呆症、帕金森病和亨廷顿氏病。研究发现水杨酸的一个分子组件可与3 -磷酸甘油醛脱氢酶(GAPDH)结合,而GAPDH是老年痴呆症、帕金森病和亨廷顿氏病的罪魁祸首。

GAPDH是葡萄糖代谢过程中的关键酶,在细胞中还担任其他重要的角色如信号传导等。氧化应激被认为是导致这些疾病的主要原因,氧化应激会导致过多的自由基和其他活性化合物。GAPDH在这种条件下被修改并进入细胞核,增强蛋白质的周转从而导致细胞死亡。治疗帕金森病的药物deprenyl就是通过阻止GAPDH进入细胞核起作用。

水杨酸阻止GAPDH进入细胞核

汤普森研究所及约翰霍普金斯大学的研究人员通过高通量筛选确定人体中与水杨酸结合的蛋白质。研究人员发现水杨酸可绑定GAPDH阻止其进入细胞核,研究人员还发现其他两种物质与GAPDH结合比水杨酸效果更好。其中一种物质是甘草中水杨酸的自然衍生物,另外一种是实验室合成的衍生物。

今年早些时候,Klessig研究小组确定了另外一种水杨酸的靶向目标蛋白,称为高速迁移组1(HMGB1),这种蛋白可导致炎症,并与几种疾病有关,包括关节炎、红斑狼疮、脓毒症、动脉粥样硬化和某些癌症。低水平的水杨酸可抑制这些炎症,水杨酸衍生物对这些炎症的抑制作用是水杨酸的40-70倍。

Klessig表示,理解水杨酸及其衍生物如何调节 GAPDH和HMGB1,水杨酸自然衍生物及合成衍生物的发现,为水杨酸治疗各种流行病带来新希望。

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