Development of therapy targeting dysregulation of cell cycle and JNK pathway in polyglutamine diseases

开发针对多聚谷氨酰胺疾病中细胞周期和 JNK 通路失调的治疗方法

• 批准号: 23390230
• 负责人: KATSUNO MASAHISA
• 金额: $ 12.4万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390230/
• 关键词: ポリグルタミン病; 球脊髄性筋萎縮症; 神経変性; 細胞周期; JNK; 運動ニューロン; サイクリン依存性キナーゼ; ポリグルタミン; マイクロアレイ; 神経変性疾患; CGRP1; naratriptan; 転写障害; 神経ペプチド; セロトニン受容体

Polyglutamine diseases are a group of hereditary neurodegenerative disorders caused by an expansion of genomic CAG trinucleotide expansion. Intra-neuronal accumulation of causative protein is construed as a pivotal molecular event in the pathogenesis of polyglutamine diseases. Our study demonstrated that dysregulation of cell cycle and abnormal activation of JNK pathway underlie the motor neuron degeneration in spinal and bulbar muscular atrophy (SBMA). We also showed that pharmacological suppression of JNK ameliorates polyglutamine-mediated neurodegeneration in SBMA.

多聚谷氨酰胺病是一组由基因组CAG三核苷酸扩增引起的遗传性神经退行性疾病。致病蛋白在神经元内的蓄积被认为是多聚谷氨酰胺疾病发病机制中的关键分子事件。我们的研究表明，细胞周期失调和JNK通路的异常激活是脊髓延髓肌萎缩症（SBMA）运动神经元变性的基础。我们还发现，药理学抑制JNK改善SBMA中聚谷氨酰胺介导的神经变性。

项目成果

Genistein, a natural product derived from soybeans, ameliorates polyglutamine‐mediated motor neuron disease

• DOI: 10.1111/jnc.12172
• 发表时间: 2013-07
• 期刊: Journal of Neurochemistry
• 影响因子: 4.7
• 作者: Qiang Qiang-Qiang;H. Adachi;Zhe Huang;Yue‐Mei Jiang;M. Katsuno;Makoto Minamiyama;H. Doi;Shin-jiro Matsumoto-Shin-j

Cell cycle dysregulation in motor neurons of spinal and bulbar muscular atrophy (SBMA)

脊髓和延髓肌萎缩症 (SBMA) 运动神经元的细胞周期失调

• 发表时间: 2012
• 作者: Katsuno M;Adachi H;Kondo N;Minamiyama M;Doi H;Matsumoto S;Miyazaki Y;Iida M;Nakatsuji H;Tanaka F;Sobue G
• 通讯作者: Sobue G

Heat shock factor-1(Hsf-1) influences distribution of pathogenic androgen receptor aggregations in model mouse of spinal and bulbar muscular atrophy (SBMA)

热休克因子-1（Hsf-1）影响脊髓和延髓肌萎缩症（SBMA）模型小鼠致病性雄激素受体聚集的分布

• 发表时间: 2011
• 作者: Kondo N;Katsuno M;Adachi H;Minamiyama M;Doi H;Matsumoto S-J;Miyazaki Y;Tanaka F;Sobue G
• 通讯作者: Sobue G

Neurobiological Study of Postmortem Brain from Brain Bank : for the study of spinal disorders

脑库死后大脑的神经生物学研究：用于脊柱疾病的研究

• 发表时间: 2013
• 作者: Katsuno M.

CGRP1 is the new therapeutic target for SBMA (Spinal and Bulbar Muscular Atrophy)

CGRP1 是 SBMA（脊髓和延髓肌萎缩症）的新治疗靶点

• 发表时间: 2012
• 作者: Minamiyama M;Katsuno M;Adachi H;Doi H;Kondo N;Iida M;Ishigaki S;Fujioka Y;Matsumoto S;Miyazaki Y;Tanaka F;Kurihara H;Sobue G.
• 通讯作者: Sobue G.