Increased autophagy in transgenic mice with a G93A mutant SOD1 gene

Morimoto, Nobutoshi; Nagai, Makiko; Ohta, Yasuyuki; Miyazaki, Kazunori; Kurata, Tomoko; Morimoto, Mizuki; Murakami, Tetsuro; Takehisa, Yasushi; Ikeda, Yoshio; Kamiya, Tatsushi; Abe, Koji

doi:10.1016/j.brainres.2007.06.045

Cited by 223Amyotrophic Lateral Sclerosis ResearchAutophagy in Disease and TherapyAlzheimer's disease research and treatments

Increased autophagy in transgenic mice with a G93A mutant SOD1 gene

Morimoto, Nobutoshi, Nagai, Makiko, Ohta, Yasuyuki, Miyazaki, Kazunori, Kurata, Tomoko, Morimoto, Mizuki, Murakami, Tetsuro, Takehisa, Yasushi +3 more·2007·Brain Research

DOI 10.1016/j.brainres.2007.06.045

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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.

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Many studies in cellular and animal models of ALS indicate enhanced autophagy activity in ALS.
“Many studies in cellular and animal models of ALS indicate enhanced autophagy activity in ALS (Morimoto et al., 2007; Sasaki, 2011), in addition to the occurrence of autophagy-mediated clearance of mutant SOD1 and TDP-43 (Nassif et al., 2010).”
From Downregulation of MicroRNA-193b-3p Promotes Autophagy and Cell Survival by Targeting TSC1/mTOR Signaling in NSC-34 Cells (2017) · cites this paper as Morimoto et al., 2007
Reduced levels of active/phosphorylated markers of the MTOR pathway suggest autophagy induction in SOD1G93A mice.
“reduced levels of active/phosphorylated markers of the MTOR pathway [337] suggest autophagy induction.”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [337]
In a SOD1G93A transgenic mouse model of ALS, motor neurons of symptomatic animals show increased levels of LC3-II and autophagic vacuoles compared to controls or pre-symptomatic mice.
“In a SOD1G93A transgenic mouse model of ALS, motor neurons of symptomatic animals show increased levels of LC3-II and autophagic vacuoles compared to controls or pre-symptomatic mice.”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [337]

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Authors: Morimoto, N., Nagai, M., Ohta, Y., Miyazaki, K., Kurata, T., Morimoto, M., Murakami, T., Takehisa, Y., Ikeda, Y., Kamiya, T., & Abe, K.
Affiliations: Okayama University (JP)
Corresponding author: Abe, Koji
ORCID: Nagai, Makiko
Ohta, Yasuyuki
Takehisa, Yasushi
Ikeda, Yoshio
Abe, Koji
Venue: Brain Research
Publisher: Elsevier BV
Published: 2007-09
Volume: 1167
Pages: 112-117
ISSN: 0006-8993 (ISSN-L)
DOI: 10.1016/j.brainres.2007.06.045
OpenAlex: W2078018384
Cited by: 223
References: 32
Citations by year: 2026: 3 · 2025: 8 · 2024: 7 · 2023: 6 · 2022: 4 · 2021: 14 · 2020: 14 · 2019: 10 · 2018: 11 · 2017: 19 · 2016: 17 · 2015: 22 · 2014: 14 · 2013: 17 · 2012: 16
FWCI: 6.65
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Brain Research (publishedVersion)
PubMed (publishedVersion)
Funders: Ministry of Education, Culture, Sports, Science and Technology
Ministry of Health, Labour and Welfare
Topics: Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords: autophagy, amyotrophic lateral sclerosis, SOD1 G93A mice, LC3-II, mTOR signaling, motor neurons, protein accumulation, autophagosome formation, ubiquitin-proteasome system
MeSH terms: Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis, Animals, Autophagy, Central Nervous System, Disease Models, Animal, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Microtubule-Associated Proteins, Motor Neurons, Mutation, Nerve Degeneration, Nerve Tissue Proteins, Phosphorylation, Protein Kinases, Serine, Spinal Cord, Superoxide Dismutase, Up-Regulation, Genetic Predisposition to Disease, Mice, TOR Serine-Threonine Kinases

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Increased autophagy in transgenic mice with a G93A mutant SOD1 gene

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