Activation of STAT3 and inhibitory effects of pioglitazone on STAT3 activity in a mouse model of SOD1-mutated amyotrophic lateral sclerosis

Neuropathology : Official Journal of the Japanese Society of Neuropathology
Noriyuki ShibataMakio Kobayashi

Abstract

Signal transducer and activator of transcription-3 (STAT3) is a member of the proinflammatory transcription factor STAT family. Several studies have documented implications for neuroinflammation in amyotrophic lateral sclerosis (ALS). We recently demonstrated activation of STAT3 in spinal cords obtained at autopsy from sporadic ALS patients. To determine the involvement of STAT3 and effects of pioglitazone on STAT3 activity in familial ALS with superoxide dismutase-1 (SOD1) mutation, we performed immunoblot and immunohistochemical analyses of the active form of STAT3 (p-STAT3) in spinal cords from mice overexpressing mutant SOD1 (ALS mice) and nontransgenic littermates (control mice). Immunoblot analysis delineated significant increases in nuclear p-STAT3 levels in non-treated ALS mice as compared with pioglitazone-treated ALS mice and non-treated and pioglitazone-treated control mice. Immunohistochemical analysis revealed prominent p-STAT3 accumulations in the nucleus of motor neurons, reactive astrocytes and activated microglia in non-treated ALS mice but not pioglitazone-treated ALS mice and non-treated and pioglitazone-treated control mice. The present results provide in vivo evidence for increased phosphorylative activatio...Continue Reading

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Jun 1, 2012·Expert Opinion on Drug Discovery·Marcie A Glicksman
Aug 19, 2015·Frontiers in Cellular Neuroscience·Lucile Ben HaimCarole Escartin
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Jun 28, 2019·Frontiers in Immunology·Neibla Priego, Manuel Valiente
Jun 6, 2019·Aging and Disease·Kunyu LiSong Qin
Jun 30, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xue-Bin ZhaoJun Yang

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