Cystamine protects from 3-nitropropionic acid lesioning via induction of nf-e2 related factor 2 mediated transcription.
Cystamine protects from 3-nitropropionic acid lesioning via induction of nf-e2 related factor 2 mediated transcription.
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DOI：
10.1016/j.expneurol.2010.04.008
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发表时间：
2010-07
影响因子：
5.3
通讯作者：
Johnson, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Calkins, Marcus J.;Townsend, Jessica A.;Johnson, Delinda A.;Johnson, Jeffrey A.
已知胱胺的全身给药可保护神经毒性的化学和遗传模型。尽管在实验室模型中具有积极作用，但胱胺尚未成功转化为神经退行性疾病的临床应用。此外，胱胺通过组织转氨酶抑制来保护的长期假设最近受到了挑战。这里描述的研究检查其他潜在的机制，试图揭示神经退行性疾病治疗的分子靶点，胱胺介导的保护。基于先前描述的胱胺的作用，我们研究了通过抗氧化反应元件（ARE）激活NF-E2相关因子2（Nrf 2）介导的信号传导的潜力。我们发现，胱胺激活Nrf 2/ARE在细胞培养和脑组织中，然后探讨在细胞培养中激活的机制。在活体动物中，我们发现3-硝基丙酸（3 NP）毒性的神经保护作用是Nrf 2依赖性的。因此，这些发现提供了强有力的证据，表明Nrf 2信号可能是预防神经退行性变的有效靶点。
Systemic administration of cystamine is known to protect from both chemical and genetic models of neurotoxicity. Despite positive effects in laboratory models, cystamine has not been successfully translated to clinical application for neurodegenerative disease. Furthermore, the long held assumption that cystamine protects through tissue-transglutaminase inhibition has recently been challenged. The studies described here examine other potential mechanisms of cystamine-mediated protection in an attempt to reveal molecular targets for neurodegenerative therapy. Based on previously described effects of cystamine, we examined the potential for activation of NF-E2 related factor 2 (Nrf2) mediated signaling through the antioxidant response element (ARE). We found that cystamine activates Nrf2/ARE both in cell culture and in brain tissue and then probed the mechanism of activation in cell culture. In live animals, we show that neuroprotection from 3-nitropropionic acid (3NP) toxicity is Nrf2-dependent. Therefore, these findings provide strong evidence that Nrf2 signaling may be an effective target for prevention of neurodegeneration.
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影响因子：
4.7
作者：
Kraft, Andrew D.;Lee, Jong-Min;Johnson, Jeffrey A.
通讯作者：
Johnson, Jeffrey A.
DOI：
10.1073/pnas.0813361106
发表时间：
2009-02-24
影响因子：
11.1
作者：
Chen, Pei-Chun;Vargas, Marcelo R.;Johnson, Jeffrey A.
通讯作者：
Johnson, Jeffrey A.
影响因子：
4.3
作者：
Kumar, Puneet;Kumar, Anil
通讯作者：
Kumar, Anil
影响因子：
4.8
作者：
Lee, JM;Shih, AY;Johnson, JA
通讯作者：
Johnson, JA
影响因子：
5.2
作者：
Johnson, Jeffrey A.;Johnson, Delinda A.;Kraft, Andrew D.;Calkins, Marcus J.;Jakel, Rebekah J.;Vargas, Marcelo R.;Chen, Pei-Chun
通讯作者：
Chen, Pei-Chun