Neuroprotective copper bis(thiosemicarbazonato) complexes promote neurite elongation.
Neuroprotective copper bis(thiosemicarbazonato) complexes promote neurite elongation.
复制标题
神经保护性铜双（硫代血症核心）络合物可促进神经突伸长。
DOI：
10.1371/journal.pone.0090070
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
White AR
中科院分区：
文献类型：
--
作者：
Bica L;Liddell JR;Donnelly PS;Duncan C;Caragounis A;Volitakis I;Paterson BM;Cappai R;Grubman A;Camakaris J;Crouch PJ;White AR
生物金属稳态异常是许多神经退行性疾病的核心特征，包括阿尔茨海默病 (AD)、帕金森病 (PD) 和运动神经元病。最近的研究表明，作为离子载体的金属络合化合物（例如氯碘羟喹和 PBT2）在神经退行性疾病的动物模型中具有强大的治疗活性；然而，神经保护作用的机制仍不清楚。这些神经保护或神经生成过程可能与金属离子载体传递或重新分布生物金属（例如铜和锌）有关。为了进一步研究这一点，我们研究了双（氨基硫脲）-铜复合物 CuII(gtsm) 对 PC12 神经元相关培养物中神经突发生和神经突伸长（神经生成结果）的影响。我们发现，当以 25 或 50 nM 的浓度过夜递送时，CuII(gtsm) 会诱导 PC12 细胞中神经突的强烈伸长。使用替代的双(氨基硫脲)铜配合物 CuII(atsm) 也观察到了类似的效果，但浓度较高。 CuII(gtsm) 诱导的神经突伸长仅限于长度范围为 75-99 µm 的神经突，50 nM CuII(gtsm) 处理后，该长度范围内的神经突数量增加了 2.3 倍。研究了神经再生作用的机制并揭示了 CuII(gtsm) 抑制细胞磷酸酶活性。与 50 nM CuII(gtsm) 相比，用 5 nM FK506（钙调神经磷酸酶抑制剂）处理培养物会导致类似的神经突伸长，这表明 CuII(gtsm) 介导的磷酸酶抑制与神经再生结果之间存在潜在联系。
Abnormal biometal homeostasis is a central feature of many neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and motor neuron disease. Recent studies have shown that metal complexing compounds behaving as ionophores such as clioquinol and PBT2 have robust therapeutic activity in animal models of neurodegenerative disease; however, the mechanism of neuroprotective action remains unclear. These neuroprotective or neurogenerative processes may be related to the delivery or redistribution of biometals, such as copper and zinc, by metal ionophores. To investigate this further, we examined the effect of the bis(thiosemicarbazonato)-copper complex, CuII(gtsm) on neuritogenesis and neurite elongation (neurogenerative outcomes) in PC12 neuronal-related cultures. We found that CuII(gtsm) induced robust neurite elongation in PC12 cells when delivered at concentrations of 25 or 50 nM overnight. Analogous effects were observed with an alternative copper bis(thiosemicarbazonato) complex, CuII(atsm), but at a higher concentration. Induction of neurite elongation by CuII(gtsm) was restricted to neurites within the length range of 75–99 µm with a 2.3-fold increase in numbers of neurites in this length range with 50 nM CuII(gtsm) treatment. The mechanism of neurogenerative action was investigated and revealed that CuII(gtsm) inhibited cellular phosphatase activity. Treatment of cultures with 5 nM FK506 (calcineurin phosphatase inhibitor) resulted in analogous elongation of neurites compared to 50 nM CuII(gtsm), suggesting a potential link between CuII(gtsm)-mediated phosphatase inhibition and neurogenerative outcomes.
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缺氧成像剂CUII（ATSM）具有神经保护作用，并改善了帕金森氏病多种动物模型的运动和认知功能。
DOI：
10.1084/jem.20112285
发表时间：
2012-04-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hung LW;Villemagne VL;Cheng L;Sherratt NA;Ayton S;White AR;Crouch PJ;Lim S;Leong SL;Wilkins S;George J;Roberts BR;Pham CL;Liu X;Chiu FC;Shackleford DM;Powell AK;Masters CL;Bush AI;O'Keefe G;Culvenor JG;Cappai R;Cherny RA;Donnelly PS;Hill AF;Finkelstein DI;Barnham KJ
通讯作者：
Barnham KJ
影响因子：
--
作者：
Kaden D;Bush AI;Danzeisen R;Bayer TA;Multhaup G
通讯作者：
Multhaup G
DOI：
10.1002/neu.20114
发表时间：
2005-04-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Birkaya, B;Aletta, JM
通讯作者：
Aletta, JM
DOI：
10.1073/pnas.1116227108
发表时间：
2012-01-03
影响因子：
11.1
作者：
Donnelly, Paul S.;Liddell, Jeffrey R.;Crouch, Peter J.
通讯作者：
Crouch, Peter J.
影响因子：
3.8
作者：
Hidalgo, J;Aschner, M;Vasák, M
通讯作者：
Vasák, M