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4-octyl itaconate ameliorate cognitive impairment in 3xTg mouse model of Alzheimer's Disease

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The most prevalent form of dementia, Alzheimer's disease (AD), is characterized by abnormal amyloid-(A) plaque accumulation, neuroinflammation, and neuronal loss. A cell-permeable derivative of itaconate called 4-octyl itaconate (OI) has… Click to show full abstract

The most prevalent form of dementia, Alzheimer's disease (AD), is characterized by abnormal amyloid-(A) plaque accumulation, neuroinflammation, and neuronal loss. A cell-permeable derivative of itaconate called 4-octyl itaconate (OI) has recently been shown to reduce inflammation. However, the impact of OI in the 3xTg transgenic mouse model of AD is still unclear. We administered OI or saline to 3xTg-AD mice. According to our findings, OI improved cognitive functions. OI also significantly decreased brain Aβ deposition and Aβ levels, inhibited cell apoptosis, decreased hippocampal and cortical neuronal damage. Additionally, we discovered that OI decreased the levels of proinflammatory cytokines, cell apoptosis, and cognitive decline in the brains of 3xTg-AD mice while increasing the expression of the Nrf2/HO-1 signaling pathway in 3xTg-AD mice, suggesting that OI might be recognized as a promising candidate for the treatment of AD. TPA 971566-AHA This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Keywords: octyl itaconate; itaconate; alzheimer disease; physiology; mouse model

Journal Title: Physiology
Year Published: 2023

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