Morimoto Nobutoshi, Nagai Makiko, Ohta Yasuyuki, Miyazaki Kazunori, Kurata Tomoko, Morimoto Mizuki, Murakami Tetsuro, Takehisa Yasushi, Ikeda Yoshio, Kamiya Tatsushi, Abe Koji
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Brain Res. 2007 Sep 5;1167:112-7. doi: 10.1016/j.brainres.2007.06.045. Epub 2007 Jul 7.
Autophagy, like the ubiquitin-proteasome system, is considered to play an important role in preventing the accumulation of abnormal proteins. Rat microtubule-associated protein 1 light chain 3 (LC3) is important for autophagy, and the conversion from LC3-I into LC3-II is accepted as a simple method for monitoring autophagy. We examined a SOD1G93A transgenic mouse model for amyotrophic lateral sclerosis (ALS) to consider a possible relationship between autophagy and ALS. In our study we analyzed LC3 and mammalian target of rapamycin (mTOR), a suppressor of autophagy, by immunoassays. The level of LC3-II, which is known to be correlated with the extent of autophagosome formation, was increased in SOD1G93A transgenic mice at symptomatic stage compared with non-transgenic or human wild-type SOD1 transgenic animals. Moreover, the ratio of phosphorylated mTOR/Ser2448 immunopositive motor neurons to total motor neurons was decreased in SOD1G93A-Tg mice. The present data show the possibility of increased autophagy in an animal model for ALS. And autophagy may be partially regulated by an mTOR signaling pathway in these animals.
与泛素 - 蛋白酶体系统一样，自噬被认为在防止异常蛋白质积累方面发挥着重要作用。大鼠微管相关蛋白1轻链3（LC3）对自噬很重要，并且从LC3 - I转化为LC3 - II被认为是监测自噬的一种简单方法。我们研究了肌萎缩侧索硬化症（ALS）的SOD1G93A转基因小鼠模型，以探讨自噬与ALS之间可能的关系。在我们的研究中，我们通过免疫测定分析了LC3和自噬抑制因子雷帕霉素靶蛋白（mTOR）。已知与自噬体形成程度相关的LC3 - II水平，在有症状阶段的SOD1G93A转基因小鼠中比非转基因或人类野生型SOD1转基因动物更高。此外，在SOD1G93A - Tg小鼠中，磷酸化mTOR / Ser2448免疫阳性运动神经元与总运动神经元的比例降低。目前的数据表明在ALS动物模型中自噬增加的可能性。并且在这些动物中，自噬可能部分受mTOR信号通路调节。
