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

Autor: Jing Xiong, Dong-Lin Lu, Bai-Qiang Chen, Tong-Yun Liu, Zi-Xuan Wang
Rok vydání: 2022
Předmět:
Zdroj: NeuroMolecular Medicine.
ISSN: 1559-1174
1535-1084
DOI: 10.1007/s12017-022-08725-y
Popis: 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.
Databáze: OpenAIRE
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