title: Increased autophagy in transgenic mice with a G93A mutant SOD1 gene.
abstract: 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.
authors: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors: Nobutoshi
authors: N
authors: Morimoto
authors: Makiko
authors: M
authors: Nagai
authors: Yasuyuki
authors: Y
authors: Ohta
authors: Kazunori
authors: K
authors: Miyazaki
authors: Tomoko
authors: T
authors: Kurata
authors: Mizuki
authors: M
authors: Morimoto
authors: Tetsuro
authors: T
authors: Murakami
authors: Yasushi
authors: Y
authors: Takehisa
authors: Yoshio
authors: Y
authors: Ikeda
authors: Tatsushi
authors: T
authors: Kamiya
authors: Koji
authors: K
authors: Abe
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D002490:Central Nervous System / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000032:analysis / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D058570:TOR Serine-Threonine Kinases; D015854:Up-Regulation / Q000502:physiology
chemical_list: C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C000606290:SOD1 protein, human; D012694:Serine; C000606291:Sod1 protein, mouse; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases