Rapamycin is a neuroprotective treatment for traumatic brain injury
Rapamycin is a neuroprotective treatment for traumatic brain injury
复制标题
DOI：
10.1016/j.nbd.2006.12.003
复制
发表时间：
2007-04-01
影响因子：
6.1
通讯作者：
Pinkas-Kramarski, R.
中科院分区：
文献类型：
--
作者：
Erlich, S.;Alexandrovich, A.;Pinkas-Kramarski, R.
雷帕霉素的哺乳动物靶标，通常称为mTOR，是调节翻译和细胞分裂的丝氨酸/苏氨酸激酶。mTOR整合来自多个上游信号的输入，包括生长因子和营养素以调节蛋白质合成。mTOR的抑制导致细胞周期停滞、细胞增殖抑制、免疫抑制和自噬诱导。自噬是蛋白质合成和降解之间的平衡过程，是一种亚细胞成分的大量降解，在氨基酸剥夺时被诱导。雷帕霉素，mTOR信号传导抑制剂，模拟氨基酸，并在一定程度上，生长因子剥夺。在本研究中，我们检查了雷帕霉素对脑损伤后小鼠结局的影响。我们的研究结果表明，雷帕霉素注射4小时后，闭合性脑损伤显着改善功能恢复表现为神经严重程度评分，神经行为测试的变化。为了验证注射的雷帕霉素的活性，我们证明了它抑制p70 S6 K磷酸化，减少小胶质细胞/巨噬细胞活化，并增加损伤部位存活神经元的数量。因此，我们认为，雷帕霉素是神经保护创伤性脑损伤后，作为一种药物在临床上用于其他适应症，我们建议，雷帕霉素应进行进一步的研究，以考虑它作为一种新的治疗创伤性脑损伤。(c)2007年爱思唯尔公司All rights reserved.
The mammalian target of rapamycin, commonly known as mTOR, is a serine/threonine kinase that regulates translation and cell division. mTOR integrates input from multiple upstream signals, including growth factors and nutrients to regulate protein synthesis. Inhibition of mTOR leads to cell cycle arrest, inhibition of cell proliferation, immunosuppression and induction of autophagy. Autophagy, a bulk degradation of sub-cellular constituents, is a process that keeps the balance between protein synthesis and protein degradation and is induced upon amino acids deprivation. Rapamycin, mTOR signaling inhibitor, mimics amino acid and, to some extent, growth factor deprivation. In the present study we examined the effect of rapamycin, on the outcome of mice after brain injury. Our results demonstrate that rapamycin injection 4 h following closed head injury significantly improved functional recovery as manifested by changes in the Neurological Severity Score, a neurobehavioral testing. To verify the activity of the injected rapamycin, we demonstrated that it inhibits p70S6K phosphorylation, reduces microglia/macrophages activation and increases the number of surviving neurons at the site of injury. We therefore suggest that rapamycin is neuroprotective following traumatic brain injury and as a drug used in the clinic for other indications, we propose that further studies on rapamycin should be conducted in order to consider it as a novel therapy for traumatic brain injury. (c) 2007 Elsevier Inc. All rights reserved.