演題詳細
Poster
ポリグルタミン病、ALS、脊髄小脳変性症、その他の神経変性疾患
Polyglutamine Diseases, ALS, SCD, Other Neurodegenerative Disorder
開催日 | 2014/9/11 |
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時間 | 11:00 - 12:00 |
会場 | Poster / Exhibition(Event Hall B) |
ピオグリタゾンの球脊髄性筋萎縮症に対する効果について
Pioglitazone suppresses neuronal and muscular degeneration caused by polyglutamine-expanded androgen receptors
- P1-319
- 飯田 円 / Madoka Iida:1 勝野 雅央 / Masahisa Katsuno:1 中辻 秀朗 / Hideaki Nakatsuji:1 足立 弘明 / Hiroaki Adachi:2 近藤 直英 / Naohide Kondo:1 宮崎 雄 / yu Miyazaki:1 藤内 玄規 / Genki Tohnai:1 渡辺 宏久 / Hirohisa Watanabe:1 山本 正彦 / Masahiko Yamamoto:3 岸田 堅 / Ken Kishida:4 祖父江 元 / Gen Sobue:1
- 1:名古屋大学神経内科 / Dept Neurol, Nagoya Univ, Aichi, Japan 2:産業医大神経内科 / Dept Neurol, Univ of Occupational and Environmental Health, School of Medicine, Fukuoka, Japan 3:愛知学院大心身科学部健康学科 / Dept Speech Pathology and Audiology, Aichi-Gakuin Univ School of Health Science, Aichi, Japan 4:大阪大内分泌・代謝内科学 / Dept Metabolic Med, Osaka Univ, Osaka, Japan
Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by the expansion of a CAG repeat in the androgen receptor (AR) gene. Mutant AR has been postulated to alter the expression of genes important for mitochondrial function and induce mitochondrial dysfunction. Here, we show that the expression levels of peroxisome proliferator-activated receptor-γ (PPARγ), a key regulator of mitochondrial biogenesis, were decreased in mouse and cellular models of SBMA. Treatment with pioglitazone (PG), an activator of PPARγ, improved the viability of the neuronal and muscular cells expressing polyglutamine-expanded AR. The oral administration of PG also improved the behavioral and histopathological phenotypes of the transgenic mice. Furthermore, immunohistochemical and biochemical analyses demonstrated that the administration of PG suppressed oxidative stress, nuclear factor-κB (NFκB) signal activation and inflammation both in the spinal cords and skeletal muscles of the SBMA mice. The results of the present study suggest that PG has direct effects on both neuronal and muscular degeneration in SBMA and that skeletal muscle is an important target for therapies that alleviate neuromuscular symptoms of SBMA.