Mechanism for anti-AD effect of approved medicines

已批准药物的抗 AD 作用机制

• 批准号: 24659037
• 负责人: MIZUSHIMA Tohru
• 金额: $ 2.5万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659037/
• 关键词: アルツハイマー病

Transforming growth factor (TGF)-B1 stimulates this phagocytosis. We recently reported that the APP23 mouse model for AD showed fewer AD-related phenotypes when these animals were crossed with transgenic mice expressing heat shock protein (HSP) 70. We here examined the effect of geranylgeranylacetone, an inducer of HSP70 expression, on the AD-related phenotypes. Repeated oral administration of geranylgeranylacetone to APP23 mice for 9 months not only improved cognitive function but also decreased levels of AB, AB plaque deposition and synaptic loss. The treatment also up-regulated the expression of an AB-degrading enzyme and TGF-B1 but did not affect the maturation of APP and secretase activities. These outcomes were similar to those observed in APP23 mice genetically modified to overexpress HSP70. A single oral administration of geranylgeranylacetone significantly increased the level of HSP70 when AB was concomitantly injected directly into the hippocampus.

转化生长因子 (TGF)-B1 会刺激这种吞噬作用。我们最近报道，当 APP23 小鼠模型与表达热休克蛋白 (HSP) 70 的转基因小鼠杂交时，AD 小鼠模型显示出较少的 AD 相关表型。我们在此检查了香叶基香叶基丙酮（HSP70 表达诱导剂）对 AD 相关表型的影响。 对 APP23 小鼠重复口服香叶基香叶基丙酮 9 个月，不仅改善了认知功能，而且降低了 AB、AB 斑块沉积和突触损失的水平。该治疗还上调了 AB 降解酶和 TGF-B1 的表达，但不影响 APP 和分泌酶活性的成熟。 这些结果与在基因修饰过表达 HSP70 的 APP23 小鼠中观察到的结果相似。 当同时将 AB 直接注射到海马体时，单次口服香叶基香叶基丙酮可显着增加 HSP70 的水平。

项目成果

Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease

• DOI: 10.1038/ncomms3686
• 发表时间: 2013-11-01
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Tanaka, Ken-Ichiro;Ishihara, Tomoaki;Mizushima, Tohru
• 通讯作者: Mizushima, Tohru

Comparison of pharmacokinetics between loxoprofen and its derivative with lower ulcerogenic activity, fluoro-loxoprofen

洛索洛芬及其具有较低致溃疡活性的衍生物氟洛索洛芬的药代动力学比较

• 发表时间: 2013
• 期刊: Drug Metab. Pharmacokinet
• 作者: Yamakawa;N.;Suemasu;S.;Watanabe;H.;Tahara;K.;Tanaka;K.;Okamoto;Y.;Ohtsuka;M.;Maruyama;T. and Mizushima;T.
• 通讯作者: T.

Development of NSAIDs with lower gastric side effect

开发具有较低胃副作用的非甾体抗炎药

• DOI: 10.1159/000338396
• 发表时间: 2012
• 期刊: Frontier of Gastrointestinal Research
• 作者: Mizushima;T
• 通讯作者: T

Improvement of cognitive function in Alzheimer's disease model mice by genetic and pharmacological inhibition of the EP4 receptor

• DOI: 10.1111/j.1471-4159.2011.07567.x
• 发表时间: 2012-03-01
• 期刊: JOURNAL OF NEUROCHEMISTRY
• 影响因子: 4.7
• 作者: Hoshino, Tatsuya;Namba, Takushi;Mizushima, Tohru
• 通讯作者: Mizushima, Tohru

Superiority of pulmonary administration of mepenzolate bromide over other routes as treatment for chronic obstructive pulmonary disease.

• DOI: 10.1038/srep04510
• 发表时间: 2014-03-28
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Tanaka K;Kurotsu S;Asano T;Yamakawa N;Kobayashi D;Yamashita Y;Yamazaki H;Ishihara T;Watanabe H;Maruyama T;Suzuki H;Mizushima T
• 通讯作者: Mizushima T