Proteomic profiling of the substantia nigra demonstrates CNDP2 overexpression in Parkinson's disease
Proteomic profiling of the substantia nigra demonstrates CNDP2 overexpression in Parkinson's disease
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DOI：
10.1016/j.jprot.2012.02.032
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发表时间：
2012-08-03
影响因子：
3.3
通讯作者：
Burkhard, Pierre R.
中科院分区：
文献类型：
--
作者：
Licker, Virginie;Cote, Melanie;Burkhard, Pierre R.
尽管几十年的深入研究，分子事件的精确序列和介导帕金森病（PD）的退行性过程的特定蛋白质仍然没有解开。蛋白质组学策略可以提供无偏见的工具，以确定新的候选人，并探讨原始机制参与PD。从神经病理学证实的PD患者（n=3）和对照受试者（n =3）中解剖黑质丘脑部（SN）组织（其变性是PD的标志），然后进行比较2-DE分析。本研究揭示了一个子集的神经元和/或神经胶质蛋白，似乎是失调的PD和可能有助于神经变性。观察到的变化不仅巩固了广泛接受的概念周围的PD发病机制，如氧化应激和线粒体功能障碍，但也指出了新的途径。在后者中，胞质非特异性二肽酶2（CNDP 2），一个相对未知的蛋白质尚未报道与PD发病机制，被证明是增加在PD患者的SN，证实了蛋白质印迹。免疫组织化学分析表明，在SN多巴胺能神经元的细胞质中存在CNDP 2。总之，我们的研究结果支持CNDP 2在PD神经变性中的关键作用，其机制可能涉及氧化应激，蛋白质聚集或炎症。这篇文章是一个特殊问题的一部分，题为：翻译蛋白质组学。(C)2012爱思唯尔有限公司版权所有。
Despite decades of intensive investigations, the precise sequence of molecular events and the specific proteins mediating the degenerative process underlying Parkinson's disease (PD) remain unraveled. Proteomic strategies may provide unbiased tools to identify novel candidates and explore original mechanisms involved in PD. Substantia nigra pars compacta (SN) tissue, whose degeneration is the hallmark of PD, was dissected from neuropathologically confirmed PD patients (n=3) and control subjects (n=3), before being submitted to a comparative 2-DE analysis. The present study revealed a subset of neuronal and/or glial proteins that appears to be deregulated in PD and likely to contribute to neurodegeneration. Observed alterations not only consolidate well accepted concepts surrounding PD pathogenesis such as oxidative stress and mitochondrial dysfunction but also point out to novel pathways. Among the latter, cytosolic non specific dipeptidase 2 (CNDP2), a relatively unknown protein not yet reported to be associated with PD pathogenesis, was shown to be increased in the SN of PD patients, as confirmed by Western blot. Immunohistochemical analyses demonstrated the presence of CNDP2 within the cytoplasm of SN dopaminergic neurons. Altogether, our findings support a key role of CNDP2 in PD neurodegeneration, by mechanisms that could involve oxidative stress, protein aggregation or inflammation. This article is part of a Special Issue entitled: Translational Proteomics. (C) 2012 Elsevier B.V. All rights reserved.