Anti-prion activity of Brilliant Blue G.
Anti-prion activity of Brilliant Blue G.
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DOI：
10.1371/journal.pone.0037896
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kitani H
中科院分区：
文献类型：
--
作者：
Iwamaru Y;Takenouchi T;Murayama Y;Okada H;Imamura M;Shimizu Y;Hashimoto M;Mohri S;Yokoyama T;Kitani H
朊病毒病是一种致命的神经退行性疾病，目前尚无有效的治疗方法。越来越多的证据表明，P2X7离子型嘌呤能受体（P2X7R）的过度激活在几种神经退行性疾病的神经元损失的进展。这导致了同时阻断这种受体和朊病毒复制可能是朊病毒疾病的有效治疗策略的推测。我们集中在亮蓝G（BBG），一个众所周知的P2X7R拮抗剂，具有预期赋予抗朊病毒活性的化学结构，并检查其对朊病毒蛋白（PrPres）的致病性亚型在细胞和小鼠模型中的积累的抑制作用，以确定其治疗潜力。BBG分别在14.6和3.2 µM的50%抑制浓度下阻止PrPres在感染的MG 20小胶质细胞和N2a神经细胞中积累。体内施用BBG也减少了朊病毒病小鼠脑中PrPres的积累。然而，与媒介物处理的对照相比，它似乎没有减轻疾病进展，这意味着P2X7R对朊病毒疾病中的神经元变性的复杂作用。这些结果为朊病毒疾病的病理生理学提供了新的见解，并对治疗具有重要意义。
Prion diseases are fatal neurodegenerative disorders with no effective therapy currently available. Accumulating evidence has implicated over-activation of P2X7 ionotropic purinergic receptor (P2X7R) in the progression of neuronal loss in several neurodegenerative diseases. This has led to the speculation that simultaneous blockade of this receptor and prion replication can be an effective therapeutic strategy for prion diseases. We have focused on Brilliant Blue G (BBG), a well-known P2X7R antagonist, possessing a chemical structure expected to confer anti-prion activity and examined its inhibitory effect on the accumulation of pathogenic isoforms of prion protein (PrPres) in a cellular and a mouse model of prion disease in order to determine its therapeutic potential. BBG prevented PrPres accumulation in infected MG20 microglial and N2a neural cells at 50% inhibitory concentrations of 14.6 and 3.2 µM, respectively. Administration of BBG in vivo also reduced PrPres accumulation in the brains of mice with prion disease. However, it did not appear to alleviate the disease progression compared to the vehicle-treated controls, implying a complex role of P2X7R on the neuronal degeneration in prion diseases. These results provide novel insights into the pathophysiology of prion diseases and have important implications for the treatment.
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影响因子：
16.6
作者：
Goold, R.;Rabbanian, S.;Sutton, L.;Andre, R.;Arora, P.;Moonga, J.;Clarke, A. R.;Schiavo, G.;Jat, P.;Collinge, J.;Tabrizi, S. J.
通讯作者：
Tabrizi, S. J.
影响因子：
2.5
作者：
Brown, DR
通讯作者：
Brown, DR
影响因子：
6.1
作者：
Boche, Delphine;Cunningham, Colm;Perry, V. Hugh
通讯作者：
Perry, V. Hugh
影响因子：
3.4
作者：
Bolognesi, Maria Laura;Tran, Hoang Ngoc Ai;Legname, Giuseppe
通讯作者：
Legname, Giuseppe
影响因子：
5
作者：
Jeffrey, M;Halliday, WG;Fraser, JR
通讯作者：
Fraser, JR