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 | 2014/9/12 |
|---|---|
| 時間 | 11:00 - 12:00 |
| 会場 | Poster / Exhibition（Event Hall B） |
NF-κB経路を介したOptineurinのノックダウンによる神経細胞死
Optineurin suppression causes neuronal cell death via NF-κB pathway
- P2-309
- 秋月 真由美 / Mayumi Akizuki:1 山下 博史 / Hirofumi Yamashita:1 植村 健吾 / Kengo Uemura:1 丸山 博文 / Hirofumi Maruyama:2 川上 秀史 / Hideshi Kawakami:2 伊東 秀文 / Hidefumi Ito:1 高橋 良輔 / Ryosuke Takahashi:1
- 1:京都大学大学院 医学研究科 臨床神経学 / Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan 2:広島大学 原爆放射線医学研究所 分子疫学研究分野 / Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by the progressive degeneration of motor neurons in the brain and spinal cord. The cause of sporadic ALS is unknown, and there is no effective therapy. Mutations in more than 10 genes are reported to cause familial ALS. Among these genes, optineurin (OPTN) is virtually the only gene that is considered to cause classical ALS by a loss-of-function mutation.
Recently, it was reported that wild-type optineurin (OPTNWT)suppresses NF-κB-activity, but ALS-causing mutant OPTN is unable to suppress NF-κB-activity. Taken together, these results indicate that inappropriate NF-κB activation is the pathogenic mechanism underlying OPTN mutation-related ALS.
Therefore, we knocked down OPTN in neuronal cells and examined the resulting NF-κB activity and phenotype. We found that OPTN knockdown caused neuronal cell death. And then we found that NF-κB activity was increased in OPTN knockdown cells, which was consistent with the previous report that ALS-causing OPTN mutations failed to suppress NF-κB activity. We also found that proapoptotic molecules such as p53 and Bax representing downstream targets of NF-κB are elevated after OPTN knockdown cells.
These results suggest that NF-κB suppression is a promising strategy for the treatment of ALS.