Nat Commun:FDA批准的高血压药物能延缓神经退行性病变

2017-12-22 佚名 medicalxpress

UT西南医学中心的研究人员发现,FDA批准的用于治疗高血压的药物似乎通过可能模拟热量限制的细胞信号传导途径延长了蠕虫的寿命。

UT西南医学中心的研究人员发现,FDA批准的用于治疗高血压的药物似乎通过可能模拟热量限制的细胞信号传导途径延长了蠕虫的寿命。

药物肼苯哒嗪在两种秀丽隐杆线虫(蛔虫)中延长了约25%的寿命,一种是野生型,另一种则产生高水平的神经毒性蛋白,称为tau,在人中与阿尔茨海默病有关。

“这是肼苯哒嗪治疗激活NRF2 / SKN-1信号通路的第一个报道,我们发现这种药物延长了蠕虫的寿命,甚至比其他潜在的抗衰老化合物如姜黄素和二甲双胍还要好。通过测试灵活性和摆动速度来衡量,似乎能够保持健康。“UT Southwestern生物化学助理教授Hamid Mirzaei博士说。

NRF2途径保护人类细胞免受氧化应激。他说,人体保护自身免受破坏性氧自由基的能力随着年龄的增长而减少。

老年痴呆症和阿尔茨海默病和帕金森病等神经退行性疾病的标志之一是氧化应激,据认为这种氧化应激从整个生命过程中的炎症和感染性疾病累积而来,米尔扎伊博士解释说。线虫转录因子SKN-1对应于人类中的NRF2。他说,两者在各自物种对氧化应激和寿命的反应中起着举足轻重的作用。

UT Southwestern的研究人员正在寻找一种化学探针,他们可以在实验中使用这些化学探针来鉴定在衰老过程中被氧化并变得有毒的蛋白质。他们筛选的物质将穿越血脑屏障,无毒。

年龄相关的神经退行性疾病具有破坏性,由于人类寿命的延长,这些疾病正在增加。因此,开发治疗方法以尽可能保持健康是非常重要的。 Mirzaei也是AD西南大学的Peter O'Donnell Jr.脑研究所的成员,他是阿尔茨海默病和神经退行性疾病中心的研究员。

研究人员在体内(在一个有生命的生物)和在体外(在一个实验室盘)研究蠕虫,还研究了一种称为神经母细胞瘤的儿科癌症的人类细胞。与未经处理的对照相比,该药物治疗的蛔虫寿命(从15-18天增加到约20-23天)增加约25%。

他说,一系列生物化学实验的结果表明,肼苯哒嗪衍生的寿命延长依赖于蠕虫的SKN-1途径,通过似乎模拟热量限制的机制。

为了测试肼苯哒嗪在神经退行性疾病中的效力,科学家们使用高剂量的化学应激物质鱼藤酮,这种化学物质应激物与高剂量暴露于人类的帕金森病风险增加有关。他们发现肼苯哒嗪能提供相当数量的神经保护作用,Mirzaei博士说。他补充说,这种药物在阿尔茨海默氏病秀丽隐杆线虫模型中也表现出tau毒性的显著下降。

他说:“根据这些结果,我们认为肼苯哒嗪可能是治疗人类年龄相关疾病的临床试验的良好候选者,因为它也可能为老年人群提供一般健康益处。”他强调说,这项研究是有希望的第一步,但需要进一步的研究来证实。

原始出处:

Esmaeil Dehghan, Yiqiang Zhang, Bahar SaremiHydralazine, et.al. Hydralazine induces stress resistance and extends C. elegans lifespan by activating the NRF2/SKN-1 signalling pathway. Nature Communications 8

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    2018-03-08 liye789132251
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    2018-11-03 bugit
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    2018-04-09 liuli5079

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