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bioRxiv · 10.1101/2025.09.22.677813

BET protein inhibitor JQ1 reduces inflammation and hippocampal amyloid-β level without altering Tau phosphorylation in LPS-challenged adult wild-type mice

Matuszewska, M.·Cieslik, M.·Sulejczak, D.·Wilkaniec, A.·Czapski, G. A.
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Abstract

IntroductionA growing body of evidence highlights the role of infection and inflammation in the progression of Alzheimers disease (AD). In this study, we aimed to analyze the impact of JQ1, an inhibitor of bromodomain and extraterminal domain (BET) proteins, which are key readers of the epigenetic acetylation code, on AD-related gene expression changes and biochemical alterations in the hippocampus during a lipopolysaccharide (LPS)-induced systemic inflammatory response in mice. MethodsJQ1 and LPS were administered intraperitoneally to adult male wild-type C57BL/6J mice. Changes in selected general and brain-specific parameters were measured for up to 12 h. ResultsOur results demonstrated that inhibition of BET proteins reduced LPS-induced sickness behavior and time-dependent elevation of proinflammatory signaling. LPS did not significantly alter amyloid-{beta} (A{beta}) levels; however, a significant reduction in A{beta} load was observed in JQ1-treated animals overall, suggesting that BET proteins play a crucial role in regulating A{beta} levels in the brain. At the same time, JQ1 treatment did not affect LPS-induced increases in phospho-Tau levels. DiscussionOur results suggest that inhibiting BET proteins, in addition to their anti-inflammatory action, may be an effective strategy for reducing A{beta} levels in the brain. However, a mechanistic explanation of this phenomenon requires further investigation.

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Matuszewska, M., Cieslik, M., Sulejczak, D., Wilkaniec, A., Czapski, G. A.. 2025-09-22. BET protein inhibitor JQ1 reduces inflammation and hippocampal amyloid-β level without altering Tau phosphorylation in LPS-challenged adult wild-type mice. https://doi.org/10.1101/2025.09.22.677813

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