Today, tomorrow, learn English naturally. 天天自然学英语
Beyond plaques: New Alzheimer's treatment pathway discovered
Researchers have discovered that limiting a certain enzyme can have a dramatic impact in protecting against the effects of Alzheimer's disease. The finding could lead to a new class of drugs that fight the disease.
Much of the historical research into Alzheimer's disease has focused on plaques that form in the brain thanks to the accumulation of too much amyloid proteins. Recently, though, scientists have begun looking beyond the role of these proteins (which one study suggests may form in the liver) into other probable causes of the disease and its advancement. That's largely because amyloid-based plaques, while certainly a hallmark of the disease, don't seem to be a direct cause of it, as evidenced by the failure of drugs that try to target them.
In seeking another way forward, researchers at the University of Leeds (UL) and Lancaster University (LU) in the UK, turned to an Australian study that showed that having the gene for the production of an enzyme known as PDE4B was identified as a risk factor for developing Alzheimer's.
The enzyme is found in cells and is responsible for breaking down a molecule known as cyclic AMP, which is linked to many metabolic roles including the regulation of immune function and neurotransmitter synthesis. Interestingly, a 2015 study showed that limiting PDE4B expression gave mice a brainpower boost.
Once again looking at how suppressing PDE4B might affect the brain, the UK team genetically modified mice with Alzheimer's and amyloid plaques in the brain to have reduced PDE4B activity. The researchers found startling results on a number of fronts.
First, the mice with Alzheimer's and normal PDE4B expression showed memory loss when navigating a maze. But those who had the genetic modification to have less PDE4B activity showed no impairment at all. Second, the modified mice showed a normal level of glucose metabolism in their brains even though they had Alzheimer's disease (AD) and that function is usually diminished. Finally, the team observed that mice with less PDE4B activity had less inflammation in their brains than those with more of the enzyme – another hallmark of AD.
Real hope
Because all of these effects were found in mice that already had Alzheimer's – and the accompanying amyloid plaques – but had significant improvement in symptoms, the researchers say that further investigation into how to limit PDE4B in human patients with the condition could lead to new treatment pathways.
"These results offer real hope for the development of new treatments that will benefit patients with Alzheimer's disease in the future," said LU's Neil Dawson, a co-author of the study. "It was intriguing to find that reducing PDE4B activity by just 27% could dramatically rescue memory, brain function and inflammation in the AD mice. The next stage is to test whether PDE4B-inhibiting drugs have similar beneficial effects in the AD mouse model, to test their potential efficacy in Alzheimer's disease."
Study co-author Steven Clapcote from LU, says he believes the findings might also help treat dementia beyond Alzheimer's.
"Reducing the activity of the PDE4B enzyme had a profound protective effect on memory and glucose metabolism in the AD mouse model, despite these mice showing no decrease in the number of amyloid plaques in the brain," he said. "This raises the prospect that reducing PDE4B activity may protect against cognitive impairment not only in Alzheimer's disease but also in other forms of dementia, such as Huntington's disease." Huntington's is also marked by a build-up of plaques in the brain.
注释：
amyloid: n; adj
表示"淀粉体;淀粉的"，means "a non-nitrogenous food substance consisting chiefly of starch; any substance resembling starch;resembling starch"，如：Containing amyloid deposits, as an organ. 蜡样的器官等含淀粉蛋白沉积的
hallmark：n
表示"标志"，means "a distinctive characteristic or attribute"，如：One hallmark of a good politician is his ability to influence people. 衡量一个优秀政治家的标志之一就是他影响大众的能力。
cyclic：adj
表示" 循环的；周期性的"，means "conforming to the Carnot cycle"，如：Cyclic blood is the chemical compound of several kinds of substances in our blood vessel. 在我们的血管中循环的血液是几种物质的化合物
neurotransmitter: n
表示" 神经传递素"，如：A neurotransmitter must be present within the presynaptic neuron. 突触前神经元必须存在神经递质。
intriguing: adj
表示" 吸引人的；有趣的"，means "disturbingly provocative"，如：The bigger picture is more intriguing. 图片越大就越吸引人。
efficacy: n
表示" 功效"，means "capacity or power to produce a desired effect"，如：We are testing the efficacy of a new drug. 我们正在测试新药的功效。
中文简要说明：
随着高龄化社会的到来，「老年痴呆症」(阿兹海默症,Alzheimer's disease，AD)愈来愈受到关注，脑神经学家一直在探寻治疗方法。过去几年，清除淀粉样蛋白斑块的治疗方向宣告失败，似乎走到了死胡同，令各界沮丧，现在科学家从基因改造的方向下手，限制某种酵素，可能催生治疗失智症的新药物。
新阿特拉斯(New Altas)报导，阿兹海默症的大部分历史研究，都集中在类淀粉样蛋白积累过多，而在大脑中形成的斑块上。不过，科学家对此类蛋白质的了解愈来愈多，这才发现蛋白斑块仅是失智症的「症征」，却不是发病的原因。过去几年以来，针对消除蛋白斑块的药物，并不能治疗痴呆症，就证明了这一点。
英国利兹大学 (UL) 和兰卡斯特大学 (LU) 的研究人员，决定另辟蹊径。他们从澳洲发表的一篇研究论文，该研究表明，产生一种名为PDE4B酵素的基因，可能是发展为阿兹海默症的原始因素。
这种酵素普遍存在于细胞中，负责分解一种名为环腺苷酸(cyclic AMP)的分子，该分子与许多代谢作用有关，包括免疫功能的调节和神经传导物质合成，被称为细胞内信使(intracellular messenger)或第二信使(second messengers)。然而， 2015 年的一项研究表明，限制 PDE4B ，可以增强小鼠的脑力。
研究团队再次研究抑制 PDE4B，是否影响大脑效能，他们对高机率出现大脑淀粉样斑块的小鼠(俗称先天失智症小鼠)，进行基因改造，以降低PDE4 活性。研究人员发现，在许多方面都看到惊人的结果。
首先，患有类阿兹海默症，且PDE4B正常的小鼠，在走迷宫的表现，出现记忆丧失。但是，那些经过基因改造， PDE4B活性低的小鼠，走迷宫的表现则相当正常。其次，经过改造的小鼠，大脑中的葡萄糖代谢也较为正常，理论上，患有阿兹海默症，大脑中的葡萄糖代谢通常会减弱。
最后，研究小组观察到，与PDE4B活性较高的小鼠相比，PDE4B 活性较低的小鼠，大脑中的发炎情况较少，而慢性发炎，也是痴呆症的另一个特点。
由于所有这些作用，均出现在已患有类阿兹海默症，以及出现蛋白斑块的小鼠身上发现，因此研究人员非常振奋，这意味着已显示阿兹海默症初期症状的人类患者，也可能透过限制PDE4B酵素，做到改善失智状况的治疗方案。
研究共同作者、来自路易斯安那大学的克拉普科特(Steven Clapcote)表示，他相信这些发现，也可能用于治疗非阿兹海默症的其他失智症。
他说：「降低 PDE4B的活性，对已罹患AD的小鼠，在记忆和葡萄糖代谢都具保护作用，尽管这些小鼠大脑中的斑块并没有减少，但仍然减缓了大脑的伤害。」
这显示了新的治疗前景：降低 PDE4B 活性，不仅预防阿兹海默症的认知障碍，还可以预防其他形式的痴呆症，例如亨廷顿舞蹈症。亨廷顿舞蹈症的其中一种特征，就是大脑中出现斑块。
留言微信公众号《自然学英语LearnNaturally》，可咨询更多！