Mortalin: A protein associated with progression of Parkinson disease?
Mortalin: A protein associated with progression of Parkinson disease?
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DOI：
10.1097/nen.0b013e318163354a
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发表时间：
2008-02-01
影响因子：
3.2
通讯作者：
Zhang, Jing
中科院分区：
文献类型：
--
作者：
Shi, Min;Jin, Jinghua;Zhang, Jing
帕金森病（PD）是一种进行性神经退行性疾病，被认为在早期影响脑干，在晚期影响其他脑区，包括边缘系统和同皮质。有人认为，PD进展的病理特征是路易体沉积的扩散。为了鉴定参与PD进展的新蛋白质，我们从病理证实的PD患者的额叶皮层中制备亚细胞组分，这些患者处于疾病和路易体沉积的不同阶段，并且来自年龄匹配的对照组。蛋白质表达谱进行了比较，使用一个强大的定量蛋白质组学技术，称为同量异位素标记的相对和绝对定量结合质谱。发现大约200种蛋白质在不同阶段的PD患者和对照组之间的相对丰度显示出显着差异。基因本体分析表明，这些改变的蛋白质属于许多类别（例如线粒体功能和神经传递），可能与PD的发病机制密切相关。其中，死亡蛋白，一种线粒体蛋白，在晚期PD病例中减少，并使用独立技术进一步验证其减少。这些结果表明死亡蛋白在PD进展中的作用。
Parkinson disease (PD) is a progressive neurodegenerative disorder that is considered to affect the brainstem at its early stages and other brain regions, including the limbic system and isocortex, in advanced stages. It has been suggested that PD progression is characterized pathologically by the spreading of Lewy body deposition. To identify novel proteins involved in PD progression, we prepared subcellular fractions from the frontal cortex of pathologically verified PD patients at different stages of disease and Lewy body deposition and from age-matched controls. Protein expression profiles were compared using a robust quantitative proteomic technique called isobaric tagging for relative and absolute quantification in conjunction with mass spectrometry. Approximately 200 proteins were found to display significant differences in their relative abundance between PD patients at various stages and controls. Gene ontology analysis indicated that these altered proteins belonged to many categories (e.g. mitochondrial function and neurotransmission) that were likely critically involved in the pathogenesis of PD. Of those, mortalin, a mitochondrial protein, was decreased in the advanced PD cases and was further validated to be decreased using independent techniques. These results suggest a role for mortalin in PD progression.