今天闲来无事，将阿勇转的文章进行了翻译，供不懂英文的读者参考。
Published online 6 October 2010 | Nature | doi:10.1038/news.2010.518
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2010年6月10日网络出版
Damaged cell powerhouses linked to Parkinson’s
细胞动力工厂的损伤与帕金森综合征存在联系
Broken mitochondria may drive the disease, and could provide new therapeutic targets.Heidi Ledford
受损的线粒体可能引起帕金森，并且可能提供新的治疗方向。Heidi Ledford
Mitochondria defects have been linked to some cases of Parkinson’s disease.DR DAVID FURNESS, KEELE UNIVERSITY / SCIENCE PHOTO LIBRARY
线粒体缺陷已被认为与某些帕金森病例存在联系 DAVID FURNESS博士，英国基尔大学/科学图库
A painstaking analysis of more than 400 brain tissue samples has bolstered the link between Parkinson’s disease and the loss of cellular powerhouses called mitochondria.
一项艰苦的对于超过400个大脑组织样本进行的分析研究表明帕金森病和细胞动力工厂（称为线粒体）的损伤之间具有关联性。
If backed up by additional studies, the results, published today in Science Translational Medicine1, could warrant clinical trials of existing drugs (currently used to treat other diseases) that activate a key pathway able to repair and replace broken mitochondria.
如果有更多的研究提供支持，今天【科学转化医学】出版的科研结果就能够保证可以开展目前已知药物（目前用于治疗其它疾病）的临床试验，而该等临床试验将开启一条能够修补并更新受损的线粒体的重要路径。
Parkinson’s disease is a devastating condition that gradually robs its victims of muscle control. Its cause is unknown, but a complex mixture of genetic and environmental risk factors is thought to be to blame in many cases.
帕金森病是一种浙行恶化的疾病，其能够逐步地毁坏患者对其自身肌肉的控制。这种疾病的致病原因未明， 但是基因和外部环境不良因素的综合影响被认为是其致病的重要原因。
In recent years, evidence has been mounting that damaged mitochondria contribute to the neurological damage wrought by the disease. In the 1980s, a group of recreational drug users in California developed Parkinson’s-like symptoms after taking heroin contaminated with a chemical called MPTP. Later, it was learned that MPTP acts by interfering with electron transport in mitochondria — a process that is vital for energy generation. A widely used pesticide called rotenone produces similar symptoms in rats, and also interferes with mitochondrial electron transport.
近年来，有证据已经表明受到损伤的线粒体是疾病引起神经伤害的原因。在20世纪80年代，在加利福尼亚的一批偶尔吸毒的人群在吸食受到一种称为MPTP的化学物质污染的海洛因后出现了帕金森式的症状。在此之后，研究表明MPTP会干预线粒体的电子传输，而该等电子传输的过程对于能量的制造致关重要。一种广泛使用的农药鱼藤酮（rotenone）在老鼠身上也能产生类似的帕金森症状，并且会干预线粒体的电子传输。
Furthermore, some patients with a rare, genetically inherited form of Parkinson’s disease carry mutations in key genes that regulate mitochondrial function.
此外，少数基因遗传性的帕病患者在一些控制线粒体功能的关键基因上发生了基因突变。
These findings, together with data linking other neurological illnesses such as Huntington’s disease to damaged mitochondria, have fuelled interest in the idea of fixing broken mitochondria as a way to treat the conditions, says Flint Beal, a neurologist at Weill Cornell Medical College in New York who was not involved in the latest study.
Flint Beal（魏尔康奈尔医学院（纽约）的神经学家，其没有参与最新的研究）认为：该等研究结果，以及能够证明其它诸如杭廷顿氏病与受到损伤的线粒体之间的联系的数据，已经激起大家通过修补被破坏的线粒体作为一种方法治疗帕病症状作为研究思路的兴趣
"Companies are getting more and more interested in mitochondria as a therapeutic target," he says. "It’s becoming a popular approach."
他认为：医药公司越来越有兴趣将线粒体作为一种治疗目标，这种方法正在成为一种广为使用的方法。
A wide sweep
深入研究
But neurologist Clemens Scherzer of Harvard Medical School in Boston, Massachusetts — lead author on the current study — didn’t set out to study mitochondria. He and an international consortium of researchers began by profiling patterns of gene expression in diseased versus healthy brains. The team gathered data from roughly ten times more samples than had ever before been analysed in a single Parkinson’s disease study, says Scherzer, allowing his team to conduct a more sensitive sweep of gene expression changes.
但是，位于马萨诸塞州波士顿的哈佛医学院的神经学家Clemens Scherzer（目前该项研究的主要作者）并没着手研究线粒体。他和他的由国际研究学者组成的团队已开始研究在发生疾病的大脑和健康大脑之间基因表达的不同模式。Scherzer提到该研究团队开始从更多的样本中采集数据，而这次采集的样本数量是原先单一帕金森病研究采样分析数量的近10倍以上，从而可以让他的团队开展对于基因表达变化的更深入准确的研究。
The trawl through millions of data points yielded ten gene sets not previously associated with Parkinson’s disease. All are involved in mitochondrial function and energy generation.
对于数百万数据点的采集产生了10组基因，该10组基因之前并未与帕金森病联系在一起。该等基因均与线粒体运作和能量产生有关系。
What’s more, genes regulated by a single protein called PGC-1α were expressed at abnormally low levels in patients with Parkinson’s disease. Increasing the expression of that protein in rat neurons grown in culture was enough to reduce the toxic effects of MPTP and rotenone.
此外，在帕金森病人身上被单一蛋白质（PGC-1α）管理控制的基因表现出了非正常性的低水平。在养殖的老鼠神经上增加该蛋白质的显现能够足以降低MPTP和鱼藤酮（rotenone）的毒副作用。
That, says Scherzer, suggests that PGC-1α-activating drugs might stave off the damage to the brain caused by Parkinson’s disease.
Scherzer认为，上述实验表明能够激活PGC-1α的药物也许能够阻止由于帕金森病而导致的大脑损伤。
New uses for old drugs
老药新用
Such drugs have already been widely pursued as potential therapies for type 2 diabetes, and some have already been approved for that use. Avandia (rosiglitazone), a diabetes drug recently pulled from the European market because it raises the risk of heart attack, activates a key protein in the PGC-1α pathway.
上文提及的目前已知药物已被广泛用于2型糖尿病的试验性质治疗，并且某些药物已被批准正式使用。葛兰素史克公司 的文迪亚（罗格列酮）（Avandia 【rosiglitazone】)，由于该药物提高了心脏病发作的风险，近期被从欧洲市场撤下，该药物在PGC-1α方法中能够激活关键的蛋白质。
But a related drug called Actos (pioglitazone) has not been firmly linked to heart attack and remains in use. Beal says that a clinical trial to test Actos in patients with Parkinson’s disease has already been approved by regulators.
但是，另一支相关药物Actos（吡格列酮）Actos (pioglitazone)与心脏病发作并无密切地联系性，因此仍然可用。Beal说，用Actos在帕金森病人中进行临床试验已经通过相关部门的批准。
The gene expression analysis will be a valuable tool for future research, says Asa Abeliovich, a neurologist at Columbia University Medical Center in New York. But it is still unclear whether the PCG-1α pathway is specifically suppressed in Parkinson’s disease, or if that suppression is just a consequence of the widespread mitochondrial damage that is provoked when neurons become damaged, he adds.
Asa Abeliovich，纽约哥伦比亚大学医学中心的神经学家，认为对于基因表达的分析将成为未来研究的有价值的工具。但是，他补充道：到底是PCG-1α在帕金森疾病中受到了特别抑制，还是这种抑制本就是由于神经元受到伤害从而引起分布广泛的线粒体受到损伤从而导致的结果，目前仍不清楚。
Nevertheless, if targeting PGC-1α has a beneficial effect in animal models, such details may not matter in the long run. "Is it simply that all mitochondrial function is messed up — which is what it looks like — or is it that PGC-1α specifically is messed up?" he asks. "We don’t know. But you could argue, ’Who cares? We’re just trying to cure the disease.’"
无论如何，如果将PGC-1α作为目标的方法能够在动物实验中发生有益的作用，上述细节问题从长远看并不重要。“是否仅仅是所有的线粒体功能紊乱，就像它看上去的这样，还是说就是PGC-1α特定地发生功能紊乱，我们仍未所知。但是，你可以说：谁在乎呢？我们就是想把病治好。”他如此说道。
• References参考书目
1. Zheng, B. et al. Sci. Trans. Med. 2, 52ra73 (2010).
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