Development of Molecular Targeted Disease Modifying Therapy for Polyglutamine Diseases

多聚谷氨酰胺疾病分子靶向疾病修饰疗法的发展

• 批准号: 21229011
• 负责人: SOBUE Gen
• 金额: $ 101.59万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009-05-11 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21229011/
• 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; ユビキチン-プロテアゾーム系; オートファジー; 分子シャペロン; )球脊髄性筋萎縮症; ポリグルタミン; ユビキチン; プロテアソーム; ユビチキン; 転写障害; セロトニン受容体アゴニスト; calcitonin/calcitonin-related polypeptide(CGRP1); TGF-β; calcitonin; calcitonin-related poly

Spinal and bulbar muscular atrophy (SBMA)is a motor neuron disease caused by an expansion of CAG trinucleotide expansion with in the androgen receptor (AR) gene. Nuclear accumulation of mutant AR triggers the degeneration of motor neurons in SBMA. Our results indicate that autophagy plays a protective role in SBMA, and that a small compound activating both molecular chaperones and autophagy suppresses the motor neuron degeneration in this disease. We also demonstrated that exogenous supplementation of miRNA that is up-regulated in SBMA mice attenuates mutant AR-mediated motor neuron degeneration.

脊髓延髓肌萎缩症（SBMA）是一种由雄激素受体（AR）基因CAG三核苷酸扩增引起的运动神经元疾病。突变体AR的核积聚触发SBMA中运动神经元的变性。我们的研究结果表明，自噬在SBMA中起着保护作用，并且激活分子伴侣和自噬的小化合物抑制了这种疾病中的运动神经元变性。我们还证明，外源性补充在SBMA小鼠中上调的miRNA可减弱突变型AR介导的运动神经元变性。

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

球脊髄性筋萎縮症治療薬

脊髓和延髓性肌萎缩症治疗药物

• 发表时间: 2009

Phase 2 Trial of Leuprorelin in Patients with Spinal and Bulbar Muscular Atrophy

• DOI: 10.1002/ana.21540
• 发表时间: 2009-02-01
• 期刊: ANNALS OF NEUROLOGY
• 影响因子: 11.2
• 作者: Banno, Haruhiko;Katsuno, Masahisa;Sobue, Gen
• 通讯作者: Sobue, Gen

Effect of leuprorelin in patients with spinal and bulbar muscular atrophy (SBMA): a multicenter, randomized, double-blind, placebo-controlled trial.

亮丙瑞林对脊髓和延髓性肌萎缩症 (SBMA) 患者的影响：一项多中心、随机、双盲、安慰剂对照试验。

• 发表时间: 2011
• 作者: Hanafusa N;Fujita T;et al.;Banno H
• 通讯作者: Banno H

神経変性疾患のdisease-modifying therapyへの展望

神经退行性疾病疾病缓解疗法的前景

• 作者: Daniel M.German;Katsuro Inoue;Fujita T;祖父江 元
• 通讯作者: 祖父江 元