Dimethyl Itaconate Reduces Cognitive Impairment and Neuroinflammation in APPswe/PS1ΔE9 Transgenic Mouse Model of Alzheimer's Disease.

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC

ACS Applied Electronic Materials Pub Date : 2023-06-01 DOI:10.1007/s12017-022-08725-y

Jing Xiong, Dong-Lin Lu, Bai-Qiang Chen, Tong-Yun Liu, Zi-Xuan Wang

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引用次数: 6

Abstract

Alzheimer's disease (AD) is the most common type of dementia characterized by abnormal accumulation of amyloid-β (Aβ) plaques, neuroinflammation, and neuronal loss. Dimethyl itaconate (DI), a membrane-permeable derivative of itaconate, has been recently reported to limit inflammation. However, the effect of DI in the APPswe/PS1ΔE9 (APP/PS1) transgenic mouse model of AD remains unclear. We treated APP/PS1 mice with DI or saline. Our results showed that DI ameliorated the cognitive deficits of APP/PS1 mice. Further, DI significantly decreased brain Aβ deposition and Aβ levels, inhibited cell apoptosis, decreased hippocampal and cortical neuronal damage. We also found that DI promoted the expression of the Nrf2/HO-1 signaling pathway, while inhibited cognitive impairment, cell apoptosis, and the proinflammatory cytokine levels in the brains of APP/PS1 mice. Our results indicated that DI attenuated memory impairment and neuroinflammation via the Nrf2 signaling pathway in APP/PS1 mice, suggesting that DI might be recognized as a promising candidate for the treatment of AD.

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衣康酸二甲酯降低APPswe/PS1ΔE9转基因阿尔茨海默病小鼠模型的认知功能障碍和神经炎症

阿尔茨海默病(AD)是最常见的痴呆症类型，其特征是淀粉样蛋白-β (Aβ)斑块异常积聚、神经炎症和神经元丢失。衣康酸二甲酯(DI)是衣康酸的一种膜渗透衍生物，最近被报道具有限制炎症的作用。然而，DI在APPswe/PS1ΔE9 (APP/PS1)转基因AD小鼠模型中的作用尚不清楚。应用DI或生理盐水处理APP/PS1小鼠。我们的研究结果表明，DI改善了APP/PS1小鼠的认知缺陷。此外，DI显著降低脑内Aβ沉积和Aβ水平，抑制细胞凋亡，减轻海马和皮质神经元损伤。我们还发现，DI可促进APP/PS1小鼠脑内Nrf2/HO-1信号通路的表达，同时抑制APP/PS1小鼠脑内认知功能障碍、细胞凋亡和促炎细胞因子水平。我们的研究结果表明，DI通过Nrf2信号通路减轻了APP/PS1小鼠的记忆障碍和神经炎症，这表明DI可能被认为是治疗AD的有希望的候选药物。

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来源期刊

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567