Impaired antioxydative Keap1/Nrf2 system and the downstream stress protein responses in the motor neuron of ALS model mice

Brain Research
Takafumi MimotoKoji Abe

Abstract

The Kelch-like ECH-associated protein 1 (Keap1)/Nuclear erythroid 2-related factor 2 (Nrf2) system is the major cellular defense mechanism under oxidative stress, but the role in motor neuron degeneration under amyotrophic lateral sclerosis (ALS) pathology has not yet been fully elucidated. Here we examined temporal and spatial changes of Keap1, Nrf2, and their downstream stress response proteins heme oxgenase-1 (HO-1), glutathione, thioredoxin (TRX), and heat shock protein 70 (HSP70) throughout the course of motor neuron (MN) degeneration in the spinal cord of ALS model mice. Keap1 protein levels progressively decreased in the MN and anterior lumbar cord of ALS mice to 63% at early symptomatic 14 weeks and 58% at end symptomatic 18 weeks, while Nrf2 dramatically increased in the anterior lumbar cord with accumulation in the MN nucleus to 229% at 14 weeks and 471% at 18 weeks when glial like cells became also positive. In contrast, downstream stress response proteins such as HO-1, glutathione, TRX, and HSP70 showed only a small increase in MN with a significant increase to 149% to 280% in the number of glial-like cells after symptomatic 14 weeks. Our present observation suggests that MN selectively lost inductions of these impo...Continue Reading

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Citations

Aug 19, 2015·Free Radical Biology & Medicine·Delinda A Johnson, Jeffrey A Johnson
Aug 29, 2013·Oxidative Medicine and Cellular Longevity·Pamela MilaniCristina Cereda
Jun 7, 2014·Frontiers in Cellular Neuroscience·Dora Brites, Ana R Vaz
Aug 25, 2016·Molecular and Cellular Neurosciences·Alice GoodeRobert Layfield
May 29, 2013·Laboratory Investigation; a Journal of Technical Methods and Pathology·Yansu GuoChunyan Li
May 6, 2015·Molecular and Cellular Biology·Nadine BakkarRobert Bowser
Feb 13, 2020·Cells·Emiliano VicencioUte Woehlbier
Dec 20, 2018·Journal of Neuroscience Research·Yasuyuki OhtaKoji Abe
Jul 1, 2020·Neural Regeneration Research·Adriana Delice Foster, Sarah Lyn Rea
Oct 30, 2019·Life Science Alliance·Veronica GranatieroHibiki Kawamata
Jul 3, 2021·International Journal of Molecular Sciences·Elena ObradorJosé M Estrela
Jul 28, 2021·Free Radical Biology & Medicine·J Jiménez-VillegasA I Rojo

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