Upregulation of alphaB-crystallin expression in the substantia nigra of patients with Parkinson's disease
Upregulation of alphaB-crystallin expression in the substantia nigra of patients with Parkinson's disease
复制标题
帕金森病患者黑质中 αB-晶状体蛋白表达的上调。
DOI：
10.1016/j.neurobiolaging.2015.01.015
复制
发表时间：
2015-04-01
影响因子：
4.2
通讯作者：
Zhou, Jiawei
中科院分区：
文献类型：
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作者：
Liu, Yingjun;Zhou, Qinbo;Zhou, Jiawei
帕金森病(Parkinson‘s Disease，PD)是最具破坏性的神经退行性疾病之一。黑质(SN)特征性神经退行性变的潜在机制仍不完全清楚。为了更好地了解PD脑SN中发生的分子事件，我们使用基于培养衍生的同位素标签的定量蛋白质组学方法比较了PD患者和对照组黑质组织中的蛋白质表达谱。我们共鉴定了11个差异表达的蛋白质，包括α-晶体蛋白(CryAB)。验证了CryAB在SN中的表达水平和表达模式。结果表明，CryAB在帕金森病患者的SN中表达明显上调。在神经毒素诱导的小鼠帕金森病模型中，反应性星形胶质细胞和小胶质细胞中CryAB的表达也上调。此外，我们还发现在帕金森病患者脑内部分神经胶质细胞的胞浆内包涵体中，CryAB的表达增加。因此，我们发现在帕金森病患者的SN中高表达的CryAB可能参与了帕金森病患者多巴胺能神经元变性过程中的神经胶质病理过程。(C)2015 Elsevier Inc.保留所有权利。
Parkinson's disease (PD) is one of the most devastating neurodegenerative disorders. The underlying mechanisms of the characteristic neurodegeneration in the substantia nigra (SN) are still not fully understood. To better understand the molecular events occurring in the SN of PD brain, we used the culture-derived isotope tag-based quantitative proteomics to compare the protein expression profiles in the nigral tissue of PD patients and control subjects. We identified a total of 11 differentially expressed proteins, including alphaB-crystallin (Cryab). Both the levels and pattern of Cryab expression in the SN were validated. It was revealed that Cryab was markedly upregulated in the SN of PD brain. Cryab expression was also upregulated in reactive astrocytes and microglia in a neurotoxin-induced mouse PD model. Moreover, we showed increased expression of Cryab in cytoplasmic inclusions in a subset of glial cells in Parkinsonian brain. Thus, we identified Cryab that is highly expressed in the SN of PD brain and may be involved in the glial pathology during dopaminergic neuron degeneration in PD. (C) 2015 Elsevier Inc. All rights reserved.