导读：英国莱斯特大学的科学家们表示，他们已经找到了预防罹患朊病毒病的实验鼠脑细胞死亡的方法，并认为可以用来预防其他脑部疾病中大脑细胞的死亡。因此，科学家们未来有望使用单一药物来治疗诸如早老性痴呆症和帕金森氏症等一系列脑部疾病。
英找到预防脑部疾病中脑细胞死亡的方法
据英国广播公司（BBC）5月7日（北京时间）报道，英国莱斯特大学的科学家们表示，他们已经找到了预防罹患朊病毒病的实验鼠脑细胞死亡的方法，并认为可以用来预防其他脑部疾病中大脑细胞的死亡。因此，科学家们未来有望使用单一药物来治疗诸如早老性痴呆症和帕金森氏症等一系列脑部疾病。研究成果5月6日发表在《自然》杂志在线版上。
包括阿尔茨海默症、帕金森氏症、亨廷顿氏舞蹈病以及朊病毒病（如人类形式的疯牛病）等在内的很多神经变性疾病都会导致折叠错误的蛋白质堆积，进而导致脑细胞死亡。
在最新实验中，莱斯特大学的科学家们证明，在罹患朊病毒病的实验鼠身上，随着这种折叠错误的蛋白在实验鼠大脑内不断堆积，细胞会通过关闭所有新蛋白的产生来做出反应。虽然阻止新蛋白产生会让病毒停止扩散，但长时间关闭新蛋白的“制造工厂”也会使脑细胞无法获得新蛋白，从而导致脑细胞死亡。
科学家们还发现，如果向患病实验鼠的大脑内注入一种特殊的蛋白质，相应开关可以被“打开”。这时虽然脑细胞中仍有折叠错误的蛋白质堆积，但脑细胞的生命得以延长，它们与其他脑细胞之间的联系功能也能够恢复，因而患病实验鼠的生命也得到延长。
该研究的领导者乔万那•马卢奇教授接受BBC采访时表示：“最新研究结果令人激动之处在于，很多神经变性疾病都拥有相似的病理，这意味着或许能使用同样的方法治疗包括早老性痴呆症和帕金森氏症等其他脑部疾病。”
英国阿尔茨海默症研究机构的负责人艾瑞克•卡伦表示：“这个发现提出了一个非常令人激动的概念，那就是一种治疗方法可以治疗多种不同的疾病，不过，这一想法仍处于早期阶段，还需要进一步实验，在阿尔茨海默症和帕金森氏症病患上看到同样的结果才行。”
Sustained translational repression by eIF2α-P mediates prion neurodegeneration
Julie A. Moreno, Helois Radford, Diego Peretti, Joern R. Steinert, Nicholas Verity, Maria Guerra Martin, Mark Halliday, Jason Morgan, David Dinsdale, Catherine A. Ortori, David A. Barrett, Pavel Tsaytler, Anne Bertolotti, Anne E. Willis, Martin Bushell & Giovanna R. Mallucci
The mechanisms leading to neuronal death in neurodegenerative disease are poorly understood. Many of these disorders, including Alzheimer’s, Parkinson’s and prion diseases, are associated with the accumulation of misfolded disease-specific proteins. The unfolded protein response is a protective cellular mechanism triggered by rising levels of misfolded proteins. One arm of this pathway results in the transient shutdown of protein translation, through phosphorylation of the α-subunit of eukaryotic translation initiation factor, eIF2. Activation of the unfolded protein response and/or increased eIF2α-P levels are seen in patients with Alzheimer’s, Parkinson’s and prion diseases1, 2, 3, 4, but how this links to neurodegeneration is unknown. Here we show that accumulation of prion protein during prion replication causes persistent translational repression of global protein synthesis by eIF2α-P, associated with synaptic failure and neuronal loss in prion-diseased mice. Further, we show that promoting translational recovery in hippocampi of prion-infected mice is neuroprotective. Overexpression of GADD34, a specific eIF2α-P phosphatase, as well as reduction of levels of prion protein by lentivirally mediated RNA interference, reduced eIF2α-P levels. As a result, both approaches restored vital translation rates during prion disease, rescuing synaptic deficits and neuronal loss, thereby significantly increasing survival. In contrast, salubrinal, an inhibitor of eIF2α-P dephosphorylation5, increased eIF2α-P levels, exacerbating neurotoxicity and significantly reducing survival in prion-diseased mice. Given the prevalence of protein misfolding and activation of the unfolded protein response in several neurodegenerative diseases, our results suggest that manipulation of common pathways such as translational control, rather than disease-specific approaches, may lead to new therapies preventing synaptic failure and neuronal loss across the spectrum of these disorders
文献链接： https://www.nature.com/ng/journal/v44/n5/full/ng.2246.html
