Sci Transl Med：利用疾病来源iPS细胞研究帕金森氏病

7月4日，<em>Sci Transl Med</em>杂志报道了利用疾病来源诱导多能干细胞研究帕金森氏病氧化应激和线粒体功能障碍的最新进展。

帕金森氏病（PD）是一种常见的神经退行性疾病，由导致大脑黑质纹状体多巴胺能通路变性的遗传和环境因素造成的。研究者获得了来源于帕金森氏症患者和携带PINK1基因（PTEN基因诱导的假定激酶1）和LRRK2（富含亮氨酸的重复激酶2）基因突变的症状发生前个人的诱导多能干细胞（iPS细胞），并将这些细胞分别诱导产生了相应的神经细胞。研究者进而分析比较了这些神经细胞与健康对照组神经细胞的异同。

<!--more-->

研究者测量了这些iPS细胞来源的神经细胞线粒体反应几个方面的指标，包括产生的活性氧族，线粒体呼吸，质子泄漏，线粒体在神经细胞内的运动。他们还发现辅酶Q10，雷帕霉素，或LRRK2的激酶抑制剂GW5074可使来源于家族性帕金森氏症患者和高危个体iPS细胞的线粒体功能障碍获得补救。

对源于携带不同基因突变IPS细胞的神经细胞进行线粒体反应分析，为研究不同家族性PD细胞水平发病机制的共性提供了新的启示。这同时也突出了这种神经退行性疾病中的氧化应激和线粒体功能障碍的重要性。 
<div id="ztload">
<div>
<div>

<img src="http://www.bioon.com/biology/UploadFiles/201207/2012070922023531.jpg" alt="" width="113" height="149" border="0" hspace="0" />

<a title="" href="http://dx.doi.org/10.1016/j.cell.2011.10.017" target="_blank">doi:</a><a title="" href="http://stm.sciencemag.org/content/4/141/141ra90" target="_blank">10.1016/j.cell.2011.10.017</a>
PMC:
PMID:

</div>
<div>

<br/><strong>Pharmacological Rescue of Mitochondrial Deficits in iPSC-Derived Neural Cells from Patients with Familial Parkinson’s Disease</strong><br/>


Oliver Cooper1,*,?,Hyemyung Seo1,*,??,Shaida Andrabi2,?,Cristina Guardia-Laguarta3,?,John Graziotto4,?,Maria Sundberg1,?,Jesse R. McLean1,?,Luis Carrillo-Reid5,?,Zhong Xie5,?,Teresia Osborn1,?,Gunnar Hargus1,?,Michela Deleidi1,?,Tristan Lawson1,?,Helle Bogetofte1,?,Eduardo Perez-Torres1,?,Lorraine Clark3,?,Carol Moskowitz3,?,Joseph Mazzulli4,?,Li Chen2,?,Laura Volpicelli-Daley6,?,Norma Romero3,?,Houbo Jiang7,?,Ryan J. Uitti8,?,Zhigao Huang9,Grzegorz Opala10,Leslie A. Scarffe2,?,Valina L. Dawson2,?,Christine Klein11,Jian Feng7,?,Owen A. Ross8,?,John Q. Trojanowski6,?,Virginia M.-Y. Lee6,?,Karen Marder3,?,D. James Surmeier5,?,Zbigniew K. Wszolek8,?,Serge Przedborski3,?,Dimitri Krainc4,?,Ted M. Dawson2,? andOle Isacson1

Parkinson’s disease (PD) is a common neurodegenerative disorder caused by genetic and environmental factors that results in degeneration of the nigrostriatal dopaminergic pathway in the brain. We analyzed neural cells generated from induced pluripotent stem cells (iPSCs) derived from PD patients and presymptomatic individuals carrying mutations in the PINK1 (PTEN-induced putative kinase 1) and LRRK2 (leucine-rich repeat kinase 2) genes, and compared them to those of healthy control subjects. We measured several aspects of mitochondrial responses in the iPSC-derived neural cells including production of reactive oxygen species, mitochondrial respiration, proton leakage, and intraneuronal movement of mitochondria. Cellular vulnerability associated with mitochondrial dysfunction in iPSC-derived neural cells from familial PD patients and at-risk individuals could be rescued with coenzyme Q10, rapamycin, or the LRRK2 kinase inhibitor GW5074. Analysis of mitochondrial responses in iPSC-derived neural cells from PD patients carrying different mutations provides insight into convergence of cellular disease mechanisms between different familial forms of PD and highlights the importance of oxidative stress and mitochondrial dysfunction in this neurodegenerative disease.

<br/>来源：生物谷

</div>
</div>
</div>