新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » 帕金森病 » Aging Cell:天然植物化合物防止小鼠AD记忆力减退

Aging Cell:天然植物化合物防止小鼠AD记忆力减退

来源:生物谷 2014-02-11 22:36

2014年2月11日讯 /生物谷BIOON/--在水果和蔬菜比如草莓以及黄瓜中发现一种化学似乎能停止,阿尔茨海默氏病小鼠的记忆力减退,Salk生物研究所科学家近日发现。

在实验研究过程中,小鼠在出生后不到一年发展患阿尔茨海默氏症症状,每天服用一种叫做非瑟酮的黄酮醇,防止进行性记忆力和学习障碍。然而药物,并没有改变大脑中淀粉样蛋白斑。新的发现表明一种新方式来对待老年痴呆症的症状,而不是针对淀粉样蛋白斑。

我们已经表明,在正常动物中,非瑟酮能改善记忆,Pamela Maher科学家说:我们这里显示的是,它也可以影响易发生老年痴呆症的动物。

十年多前,Maher发现,非瑟酮有助于保护神经元。她和她的同事们,利用分离的细胞培养和小鼠开展研究,探讨化合物如何对大脑中细胞具有抗氧化剂和抗炎作用。最近,他们发现,非瑟酮接已知开启记忆相关的细胞途径。

非瑟酮有多个特性,当涉及到阿尔茨海默氏症可能是有益的。Maher转向阿尔茨海默氏症两个基因突变的小鼠,研究人员把这些小鼠设成一个子集,当他们只有三个月大,开始对他们的食物中增加非瑟酮。

随着小鼠的成长,研究人员以水迷宫测试他们的记忆和学习能力。九个月龄时,没有收到非瑟酮的小鼠开始在迷宫中进行更差。得到每日剂量化合物的老鼠在九个月及一岁,与正常小鼠相比没有明显差异。

与加州大学圣地亚哥分校科学家合作,Maher测试已经收到非瑟酮小鼠和未受到治疗小鼠的大脑中不同分子的水平。在阿尔茨海默氏症小鼠的症状中,他们发现,参与细胞炎症信号通路被打开。采取了非瑟酮治疗的动物,这些信号通路被挫伤,或抗炎分子发挥作用。

当非瑟酮被治疗时,一个特定的蛋白质P35,由于裂解成一个较短的版本被封锁。p35的缩短版本已知开启和断开许多其他的分子途径。该研究结果发表在Aging Cell杂志上。研究离体组织曾暗示,非瑟酮也可能减少阿尔茨海默大脑淀粉样蛋白斑的数量。

然而,上述现象并无在小鼠研究中观察到。非瑟酮并没有影响到斑块,非瑟酮似乎是作用于其他途径,那些没有被认真调查,在过去作为治疗靶点的信号途径。接下来,团队希望了解更多的关于非瑟酮如何影响记忆的分子细节。(生物谷Bioon.com)

Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer's disease transgenic mice

Currais, A., Prior, M., Dargusch, R., Armando, A., Ehren, J., Schubert, D., Quehenberger, O. and Maher, P.

Alzheimer's disease (AD) is the most common type of dementia. It is the only one of the top ten causes of death in the USA for which prevention strategies have not been developed. Although AD has traditionally been associated with the deposition of amyloid β plaques and tau tangles, it is becoming increasingly clear that it involves disruptions in multiple cellular systems. Therefore, it is unlikely that hitting a single target will result in significant benefits to patients with AD. An alternative approach is to identify molecules that have multiple biological activities that are relevant to the disease. Fisetin is a small, orally active molecule which can act on many of the target pathways implicated in AD. We show here that oral administration of fisetin to APPswe/PS1dE9 double transgenic AD mice from 3 to 12 months of age prevents the development of learning and memory deficits. This correlates with an increase in ERK phosphorylation along with a decrease in protein carbonylation, a marker of oxidative stress. Importantly, fisetin also reduces the levels of the cyclin-dependent kinase 5 (Cdk5) activator p35 cleavage product, p25, in both control and AD brains. Elevated levels of p25 relative to p35 cause dysregulation of Cdk5 activity leading to neuroinflammation and neurodegeneration. These fisetin-dependent changes correlate with additional anti-inflammatory effects, including alterations in global eicosanoid synthesis, and the maintenance of markers of synaptic function in the AD mice. Together, these results suggest that fisetin may provide a new approach to the treatment of AD.

 

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库