Testing NF-κB-based therapy in hemiparkinsonian monkeys.
Testing NF-κB-based therapy in hemiparkinsonian monkeys.
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DOI：
10.1007/s11481-012-9377-9
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发表时间：
2012-09
影响因子：
6.2
通讯作者：
Pahan, Kalipada
中科院分区：
文献类型：
--
作者：
Mondal, Susanta;Roy, Avik;Jana, Arundhati;Ghosh, Sankar;Kordower, Jeffrey H.;Pahan, Kalipada
帕金森病（PD）是影响运动、平衡、灵活性和协调性的最常见的人类神经退行性疾病。尽管进行了深入的研究，但没有有效的治疗方法可以阻止PD的发作或停止其进展。PD的灵长类动物模型被认为是人类PD的最佳可用模型之一。由于神经炎症在PD的发病机制中起着重要作用，而NF-κB作为一种促炎转录因子，参与许多促炎分子的转录，因此本研究评估了IκB激酶（IKK）α或IKKβ的NF-κB必需修饰物（NEMO）结合结构域（NBD）对应的肽对偏侧帕金森病猴多巴胺能神经元的保护能力。首先，我们发现NF-κB在1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）中毒的偏侧帕金森病猴的黑质延髓部被激活。然而，肌肉注射野生型NBD（wtNBD）肽减少了黑质NF-κB的活化和诱导型一氧化氮合酶的表达，保护了黑质纹状体轴和神经递质，并改善了偏侧帕金森病猴的运动功能。这些发现是特异性的，因为突变的NBD肽没有表现出这种作用。这些结果可能有助于将基于NF-κ B的治疗转化为PD临床。
Parkinson’s disease (PD) is the most common human neurodegenerative disorder affecting movement, balance, flexibility, and coordination. Despite intense investigation, no effective therapy is available to stop the onset PD or halt its progression. The primate model of PD is considered to be one of the best available models for human PD. Since neuroinflammation plays an important role in the pathogenesis of PD and NF-κB, a proinflammatory transcription factor, participates in the transcription of many proinflammatory molecules, this study evaluates the ability of a peptide corresponding to the NF-κB essential modifier (NEMO)-binding domain (NBD) of IκB kinase (IKK)α or IKKβ to protect dopaminergic neurons in hemiparkinsonian monkeys. First, we found that NF-κB was activated within the substantia nigra pars compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated hemiparkinsonian monkeys. However, intramuscular injection of wild type NBD (wtNBD) peptide reduced nigral activation of NF-κB and expression of inducible nitric oxide synthase, protected both the nigrostriatal axis and neurotransmitters, and improved motor functions in hemiparkinsonian monkeys. These findings were specific as mutated NBD peptide did not exhibit such effects. These results may help in the translation of NF-κB-based therapy to PD clinics.
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影响因子：
6.2
作者：
Saha, Ramendra N.;Liu, Xiaojuan;Pahan, Kalipada
通讯作者：
Pahan, Kalipada
DOI：
10.1523/jneurosci.1243-10.2010
发表时间：
2010-09-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Jana A;Pahan K
通讯作者：
Pahan K
影响因子：
11.2
作者：
Kordower, Jeffrey H.;Herzog, Christopher D.;Bartus, Raymond T.
通讯作者：
Bartus, Raymond T.
DOI：
10.1523/jneurosci.4144-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ghosh A;Roy A;Matras J;Brahmachari S;Gendelman HE;Pahan K
通讯作者：
Pahan K
影响因子：
4.8
作者：
Sriram, Krishnan;Matheson, Joanna M.;O'Callaghan, James P.
通讯作者：
O'Callaghan, James P.