Osteopontin is elevated in Parkinson's disease and its absence leads to reduced neurodegeneration in the MPTP model
Osteopontin is elevated in Parkinson's disease and its absence leads to reduced neurodegeneration in the MPTP model
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DOI：
10.1016/j.nbd.2006.10.020
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发表时间：
2007-03-01
影响因子：
6.1
通讯作者：
Nitsch, Cordula
中科院分区：
文献类型：
--
作者：
Maetzler, Walter;Berg, Daniela;Nitsch, Cordula
在帕金森病(PD)的发病机制中，涉及氧化和亚硝化应激、细胞凋亡、线粒体功能障碍和兴奋性毒性，即骨桥蛋白(OPN)也可能在其中发挥作用的过程。我们研究了帕金森病患者血清和脑脊液中OPN的浓度、其在黑质(SN)中的免疫组织化学存在情况，并在OPN缺失的小鼠中测试了该蛋白对MPTP诱导的神经退行性变的影响。帕金森病患者伴有体液中骨桥蛋白水平升高。较高的血清水平与更严重的运动症状相关。脑脊液水平与伴发性痴呆呈正相关，与多巴胺能治疗呈负相关。在人SN中，OPN表达于神经元、路易体和小胶质细胞。OPN缺陷型小鼠MPTP中毒3周后，黑质酪氨酸羟化酶阳性细胞和纹状体多巴胺能纤维的丢失明显减少。这些数据表明，OPN参与了帕金森病相关的神经退变。(C)2006 Elsevier Inc.保留所有权利。
In the pathogenesis of Parkinson's disease (PD), oxidative and nitrosative stress, apoptosis, mitochondrial dysfunction, and excitotoxicity are involved, i.e., processes in which osteopontin (OPN) may also play a role. We have studied in PD patients serum and cerebrospinal fluid (CSF) concentrations of OPN, its immunohistochemical presence in substantia nigra (SN) and tested in OPN-null mice the impact of this protein on MPTP-induced neurodegeneration. PD was accompanied by increased OPN levels in the body fluids. Higher serum levels were associated with more severe motor symptoms. CSF levels were positively associated with concomitant dementia and negatively associated with dopaminergic treatment. In human SN, OPN was expressed in neurons, in their Lewy bodies and in microglia. Loss of tyrosine-hydroxylase-positive cells in the SN and of dopaminergic fibers in the striatum was reduced 3 weeks after MPTP intoxication in OPN-null mice. These data suggest that OPN is involved in PD-associated neurodegeneration. (c) 2006 Elsevier Inc. All rights reserved.