Neuroprotective potency of anti-hyperglycemic agent 1-deoxynojirimycin

抗高血糖药 1-脱氧野尻霉素的神经保护作用

• 批准号: 21J12380
• 负责人: PARIDA ISABELLA SUPARDI
• 金额: $ 0.96万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-28 至 2023-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21J12380/
• 关键词: 1-Deoxynojirimycin; Brain insulin resistance; Alzheimer's Disease; 1-deoxynojirimycin; iminosugar; Alzheimer’s disease; brain insulin signaling; tau hyperphosphorylation

Brain insulin resistance often precedes Alzheimer’s disease (AD) long before its onset. We thereby assessed the use of 1-deoxynojirimycin (DNJ), an aza-sugar and insulin sensitizer, to relieve AD symptoms in cell culture model of neuronal insulin resistance. By assessing the changes in insulin signaling components and AD markers, we found that DNJ: 1) reverses neuronal insulin resistance by promoting AKT/GSK3B cascade: 2) attenuates tau hyperphosphorylation by inhibiting GSK3B activity (a major tau kinase) via Ser9 phosphorylation; 3) increases the expression of insulin-degrading enzyme (Ide), which may help to clear amyloid-β and lower its accumulation. Overall, this data provides novel insight into the neuroprotective mechanism of DNJ, that is, by preserving neuronal insulin sensitivity.

脑胰岛素抵抗通常在阿尔茨海默病(AD)发病前很久就出现了。因此，我们评估了氮杂糖和胰岛素增敏剂1-脱氧野生霉素(DNJ)在神经元胰岛素抵抗细胞培养模型中缓解AD症状的作用。通过评估胰岛素信号成分和AD标志物的变化，我们发现丹参：1)通过促进AKT/GSK3B级联反应来逆转神经元的胰岛素抵抗：2)通过丝氨酸9磷酸化抑制GSK3B的活性来减轻tau的过度磷酸化；3)增加胰岛素降解酶(IDE)的表达，这可能有助于清除淀粉样蛋白β并减少其积聚。总体而言，这些数据为DNJ的神经保护机制提供了新的见解，即通过保持神经元的胰岛素敏感性。

项目成果

Bioactive iminosugar 1-deoxynojirimycin reverses neuronal insulin resistance and alleviates tau hyperphosphorylation: an in vitro study using insulin-resistant neuroblastoma

生物活性亚氨基糖 1-脱氧野尻霉素可逆转神经元胰岛素抵抗并减轻 tau 蛋白过度磷酸化：一项使用胰岛素抵抗神经母细胞瘤的体外研究

• 发表时间: 2022
• 作者: Parida I. S.;Takasu S.;Ito J.;Eitsuka T.;Nakagawa K.
• 通讯作者: Nakagawa K.

1-Deoxynojirimycin exhibits neuroprotective potential via reversal of insulin resistance in an in vitro model of neuronal insulin resistance

1-Deoxynojirimycin 通过在神经元胰岛素抵抗的体外模型中逆转胰岛素抵抗而表现出神经保护潜力

• 发表时间: 2022
• 作者: Parida I. S.;Takasu S.;Ito J.;Eitsuka T.;Nakagawa K.
• 通讯作者: Nakagawa K.

Restorative effect of 1-deoxynojirimycin on neuronal insulin resistance and its beneficial implication on tau hyperphosphorylation: in-vitro study using insulin-resistant neuroblastoma

1-脱氧野尻霉素对神经元胰岛素抵抗的恢复作用及其对 tau 过度磷酸化的有益影响：使用胰岛素抵抗神经母细胞瘤的体外研究

• 发表时间: 2022
• 作者: Parida I. S.;Takasu S.;Ito J.;Eitsuka T.;Nakagawa K.
• 通讯作者: Nakagawa K.

1-Deoxynojirimycin alleviates neuronal insulin resistance and tau hyperphosphorylation in-vitro

1-脱氧野尻霉素在体外减轻神经元胰岛素抵抗和 tau 蛋白过度磷酸化

• 发表时间: 2022
• 作者: Parida I. S.;Takasu S.;Ito J.;Eitsuka T.;Nakagawa K.
• 通讯作者: Nakagawa K.

Bioactive iminosugar as nutraceutical candidate for healthy aging: focus on neuronal insulin sensitivity

生物活性亚氨基糖作为健康老龄化营养候选药物：关注神经元胰岛素敏感性

• 发表时间: 2023
• 作者: Yusheng Wang;Yonghoon Ji;Hiroshi Tsuchiya;Hajime Asama and Atsushi Yamashita;竹崎奏詠，辻勲平，ハザリカ・へマンタ，浅井光輝;Yusheng Wang;辻勲平，竹崎奏詠，浅井光輝，ハザリカ・へマンタ;Parida I. S.
• 通讯作者: Parida I. S.