Mechanism of neuroprotection by the heat shock proteins in amyotrophic lateral sclerosis model mice (SOD1-G93S transgenic mice)

热休克蛋白对肌萎缩侧索硬化症模型小鼠（SOD1-G93S转基因小鼠）的神经保护机制

• 批准号: 17590872
• 负责人: KAWAMATA Jun
• 金额: $ 2.24万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590872/
• 关键词: ALS; HSP; SOD1; Neuroprotection

1.Establishing proteome map of nervous system of ALS transgenic mice (Gurney et al. Science 1994)We have made proteome map (soluble fraction and insoluble fraction) of nervous system of young and old ALS Tg mice.2.Analysis of therapeutic effect and proteome change by administering neuroprotective HSP inducers to the ALS transgenic miceWe have administrated several possible neuroprotective drugs and analyzed proteomic change and life period, so far we could not document significant therapeutic effect of HSP inducers on ALS Tg mice3.Searching for SOD1 binding proteins using culture cellsWe searched for possible SOD1 binding protein candidates by immunoprecipitation using Neuro2A cell line. Two HSPs, HSc70 and HSP105, are found to be SOD1 binding proteins. Our finding was published on Journal of Neurochemistry.4.Possible therapeutic method based on our hypothesisWe found that HSP105 suppresses the formation of mutant SOD1 containing aggregates in cultured cell. This result suggests that techniques that raise levels of HSP105 might be promising tools for alleviation of the mutant SOD1 toxicity.

1. ALS转基因小鼠神经系统蛋白质组图谱的建立（Gurney et al.Science1994）我们制作了蛋白质组图谱2. HSP诱导剂对ALS转基因小鼠的治疗效果和蛋白质组变化分析我们给了几种可能的神经保护药物并分析了蛋白质组变化和生命周期，3.利用培养细胞寻找SOD 1结合蛋白我们利用Neuro2A细胞系，通过免疫沉淀法寻找可能的SOD 1结合蛋白候选物。HSP70和HSP105是SOD1结合蛋白。我们的研究结果发表在Journal of Neurochemistry上。4.基于我们假设的可能的治疗方法我们发现HSP 105抑制培养细胞中含有聚集体的突变SOD 1的形成。这一结果表明，提高HSP 105水平的技术可能是减轻突变SOD 1毒性的有前途的工具。

项目成果

脳神経科学イラストレイテッド 改訂第2版

神经科学图解第二修订版

• 发表时间: 2006
• 作者: 渡部 文子;真鍋 俊也
• 通讯作者: 真鍋 俊也

Heat-snock protein 105 interacts with and suppresses aggregation of mutant Cu/Zn superoxide dismutase : clues to a possible strategy for treating ALS

Heat-snock 蛋白 105 与突变型 Cu/Zn 超氧化物歧化酶相互作用并抑制其聚集：治疗 ALS 的可能策略的线索

• 发表时间: 2007
• 期刊: Journal of Neurochemistry Mar 30[Epub ahead of print]
• 作者: Yamashita H;Kawamata J;Ukawa K;Kanki R;Nakamizo T;Hatayama T;Yamanaka K;Takahashi R;Shimohama S
• 通讯作者: Shimohama S

Heat-shock protein 105 interacts with and suppresses aggregation of mutant Cu/Zn superoxide dismutase: clues to a possible strategy for treating ALS

• DOI: 10.1111/j.1471-4159.2007.04534.x
• 发表时间: 2007-09-01
• 期刊: JOURNAL OF NEUROCHEMISTRY
• 影响因子: 4.7
• 作者: Yamashita, Hirofumi;Kawamata, Jun;Shimohama, Shun
• 通讯作者: Shimohama, Shun