含基因DJ

  近日，研究表明帕金森疾病影响大脑黑质区域神经元，能够导致这一区域的线粒体活动停止甚至细胞死亡。研究者在研究中显示提供基因DJ-1的两个产品D-乳酸钠或羟乙酸盐能够阻止甚至抵消线粒体活动停止与细胞死亡这一过程，添加这两种物质到培养的海拉细胞和线虫C细胞中即可证明。线虫恢复了线粒体的活性并且阻止了神经元的退化。

他们还表明，这两种物质能够化解除草剂百草枯的毒性作用。细胞一旦被这种除草剂处理，就会导致帕金森疾病中线粒体的损害，只有添加这两种物质细胞才能恢复正常。D-乳酸钠和羟乙酸盐存在于自然未成熟的水果和某些特定的酸奶中。

Teymuras Kurzchalia和 Tony Hyman 都有马克斯普朗克研究所分子细胞生物学和遗传学的实验室及不同的研究项目——但他们都偶然发现了基因DJ-1。这种基因最初被认为是一种致癌基因，自2003年以来一直被认为与帕金森病有关联。最近的研究表明，DJ-1属于新的glyxolase家族。这些基因的主要功能被假设为替线粒体代谢中醛类副产品解毒。德累斯顿的研究小组展示DJ-1的产品，D-乳酸钠和羟乙酸盐，实际上只需要维持高线粒体跨膜电位就可以防止帕金森病中神经元的退化。

实验证明，这两种物质是神经元的“救命稻草”，添加它们到受影响的细胞中，换句话说用百草枯或衰减DJ-1处理细胞，减少除草剂的毒性作用，恢复线粒体的活性，从而确保神经元的完好。

“我们尚不清楚D-乳酸钠和羟乙酸盐如何实现这一治疗和预防效果，我们下一步将研究这一过程的分子机制，”Hyman and Kurzchalia.说。除了进一步做分子调查，他们未来也有更具体的计划，Kurzchalia说“我们可以研发一种富含D-乳酸钠的酸奶，用它来预防帕金森疾病的同时也是非常美味的!“这就是为什么研究人员提交专利申请他们的发现。

许多疾病与线粒体活性下降有关，不仅仅是帕金森疾病，因此，研究者相信DJ-1产品具有阻止细胞减少的功能。

原文摘要：

Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival

Yusuke Toyoda, Cihan Erkut, Francisco Pan-Montojo, Sebastian Boland,Martin P. Stewart, Daniel J. Müller, Wolfgang Wurst, Anthony A. Hyman,and Teymuras V. Kurzchalia

Parkinson's disease is associated with mitochondrial decline in dopaminergic neurons of the substantia nigra. One of the genes linked with the onset of Parkinson's disease, DJ-1/PARK7, belongs to a novel glyoxalase family and influences mitochondrial activity. It has been assumed that glyoxalases fulfill this task by detoxifying aggressive aldehyde by-products of metabolism. Here we show that supplying either D-lactate or glycolate, products of DJ-1, rescues the requirement for the enzyme in maintenance of mitochondrial potential. We further show that glycolic acid and D-lactic acid can elevate lowered mitochondrial membrane potential caused by silencing PINK-1, another Parkinson's related gene, as well as by paraquat, an environmental toxin known to be linked with Parkinson's disease. We propose that DJ-1 and consequently its products are components of a novel pathway that stabilizes mitochondria during cellular stress. We go on to show that survival of cultured mesencephalic dopaminergic neurons, defective in Parkinson's disease, is enhanced by glycolate and D-lactate. Because glycolic and D-lactic acids occur naturally, they are therefore a potential therapeutic route for treatment or prevention of Parkinson's disease.

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