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1、精品名师归纳总结Breaking down the barrier攻破屏障A glimmer of hope for a drug that treats disease caused by prions药物治疗朊病毒感染疾病的一线期望THE epidemic of mad-cow disease in people that some forecast in the 1990s has not, fortunately, come to pass. But Creutzfeldt-Jakob disease, to give itsproper name, is still a nasty
2、illness that humanity would be better off without.时至今日，疯牛病没有像上世纪90 岁月的某些预言说的那样在人群中流行，真是幸运。这种严肃损害人类性情的疾病的精确名称叫克雅氏病，治疗起来仍然麻烦。It is also a strange illness.克雅氏病是一种奇怪的疾玻CJD and a handful of similar neurological conditions are caused by the misfolding of a particular protein that is found in the membranes
3、 of certain nerve cells.该病以及类似的一些神经症状是由于某种神经细胞的细胞膜上的一个特殊蛋白发生错误折叠所致。The strangeness is that the misfolded protein, known as a prion, somehow catalyses other molecules of the protein to misfold in the same way.这种错误折叠的蛋白称为朊病毒，令人奇怪的是它可以催化其他蛋白分子发生相同的错误折叠，The result is a chain reaction in which more and m
4、ore protein ends up as prions.这个链式反应使越来越多的蛋白质变成朊病毒。Nerve cells containing the prions stop working. 含有朊病毒的神经细胞失去正常功能，The sufferer endures memory loss, personality changes and spontaneous, jerky bodily movements.罹患者显现记忆减退、人格转变和自发的躯体急速抽搐等症状，Eventually, the disease kills him.最终患者死亡。A drug to treat CJD w
5、ould therefore be welcome.所以，能够治疗 CJD的药物将大受青睐。可编辑资料 - - - 欢迎下载精品名师归纳总结And chemicals that seem either to prevent the misfolding, or to help the body clear away misfoldedmolecules, do, indeed, exist.能阻挡分子错误折叠或帮忙机体清除错误折叠分子的化学药品似乎的确存在， The problem is turning at least one of those chemicals into an effec
6、tive medicine.困难在于如何用至少一种这样的化学药品进行有效治疗。Adam Renslo of the University of California, San Francisco, and his colleagues have been trying to do so.旧金山加利福尼亚高校的Adam Renslo 与其同事始终在进行将化学药品用于治疗CJD的尝试，The chemicals they have lighted on are called aminothiazoles.他们感爱好的化学药品叫做氨噻唑，These are quite effective in re
7、ducing the prion levels of cultured nerve cells.它能有效降低体外培养的神经细胞内的朊病毒水平。Testing aminothiazoles in Petri dishes is, however, rather different from testing them on living animals.但是，检验发觉氨噻唑在活动物体内的作用与在体外培养细胞中的作用大不相同。A natural barrier exists between the bloodstream and the brain, to protect it from harmf
8、ul chemicals.生理状态下，血流与脑之间存在着一个屏障，使脑防止接触有害物质， This barrier interprets many putative drugs, including aminothiazoles, as harmful, and thus keeps them out.可能有效的许多药物包括氨噻唑也被这个屏障当作有害物质阻挡在脑外。And if a molecule cannot cross the barrier, it will not make an effective neurological treatment.不能通过屏障进入脑的分子当然就无法完成
9、有效的神经治疗。Dr Renslo and his colleagues have therefore been analysing and modifying the chemical structure of aminothiazoles to see if this can enable them to crossthe blood-brain barrier.为此， Renslo 博士与其同事已经在分析并尝试修饰氨噻唑的分子结构，以使之能通过血脑屏障。可编辑资料 - - - 欢迎下载精品名师归纳总结As they report in the Journal of Medicinal C
10、hemistry, they think they have now pulled off the trick.依据他们在药物化学杂志的报道，他们已经找到了突破口。They did it by removing groups of atoms called hydrogen-bond donors from the original molecules and adding a ring of carbon and hydrogen atoms.他们移除氨噻唑分子上一组供应氢键的原子，并加上一个碳氢环。修饰后的氨噻唑分子看起来更像胆固醇分子。That made the aminothiazol
11、es look more like cholesterol which despite its malign everyday reputation is an important component of brains and routinelycrosses the blood-brain barrier.尽管胆固醇成天被认为是个对人体有害的物质，但它却是脑的重要成分，是通过血脑屏障的常客。It worked.成功了！When Dr Renslo fed mice a diet containing the improved aminothiazoles, he found that th
12、e most promising of them accumulated in the brain in concentrationsnearly 25 times higher than those required to clear prions from cultured cells.Renslo 博士给小鼠喂食含有改进后的氨噻唑的饮食后，发觉这些最有期望的分子在小鼠的脑内集合，其浓度达到清除体外培养细胞内朊病毒所需浓度的25 倍。The molecular changes did not, though, seem to change the aminothiazoles prion-
13、killing attributes.氨噻唑分子的转变似乎并没有转变其杀灭朊病毒的特性。When tested in Petri dishes, the new molecules were as good as their precursors.在培养皿试验中，修饰后的分子与其前体一样有效。More importantly, preliminary results suggest they are effective at extending the lives of prion-infected mice.更重要的是，初步的试验结果提示这些分子能有效延长朊病毒感染小鼠的寿命， Such m
14、ice lived for 100 days longer when treated with the new molecules than they did when untreated.用这些新分子治疗的小鼠比不治疗的小鼠多存活100 天。That is a significant fraction of the two to three years a healthy laboratory mouse might be expected to survive if it is not experimented on.可编辑资料 - - - 欢迎下载精品名师归纳总结考虑到试验室中未受试的健
15、康小鼠的预期寿命是活期显得很显著了。2 到 3 年，染毒小鼠获得延长的这部分存Trials in mice are, of course, just the beginning. But breaching the blood-brain barrier in this way is a crucial step, and one that might be generalisedto potential treatments for other brain diseasesAlzheimers, for example.当然，用小鼠进行的试验只是个开头。但药物以这种方式突破血脑屏障的确是个关键步骤，在此基础上，人们仍可能找到治疗阿尔茨海默尔病这样的其他脑部疾病的良方。If that came to pass, this small step on the journey of drug discovery might come to be seen, in retrospect, as a giant leap.在达到那些目标之后，回过头来看，实现药物通过屏障的这一小步将被视为一个巨大的跨步。可编辑资料 - - - 欢迎下载