The Inhibition of Bromodomain and Extraterminal Domain (BET) Proteins Protects Against Microglia-Mediated Neuronal Loss In Vitro DOI Creative Commons
Marta Matuszewska, Anna Wilkaniec, Magdalena Cieślik

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 528 - 528

Published: April 4, 2025

Neuroinflammation is a key feature of all neurodegenerative disorders, including Alzheimer’s disease, and tightly regulated by epigenetic mechanisms. Among them, bromodomain extraterminal domain (BET) proteins play crucial role recognizing acetylated histones acting as transcriptional co-regulators to modulate gene expression. This study investigates the potential inhibiting BET in preventing microglia-mediated neuronal damage vitro. Murine BV2 microglial cells were exposed lipopolysaccharide (LPS) or amyloid-β (Aβ) induce an inflammatory response, subsequent effects on murine HT22 examined. tested, only Brd4 was significantly upregulated upon pro-inflammatory stimulation. JQ1, potent pan-inhibitor proteins, suppressed LPS-induced upregulation cytokine mRNA levels, Il1b, Il6, Tnf, microglia. Pre-treatment with JQ1 attenuated cytotoxicity LPS-activated toward neurons. Additionally, conditioned media from Aβ fibril-stimulated induced cell death, which partially prevented pre-treatment JQ1. Co-culture assays further demonstrated beneficial effect inhibition. Our findings suggest that targeting may offer neuroprotective strategy modulating activation, potentially providing therapeutic benefits diseases.

Language: Английский

The Inhibition of Bromodomain and Extraterminal Domain (BET) Proteins Protects Against Microglia-Mediated Neuronal Loss In Vitro DOI Creative Commons
Marta Matuszewska, Anna Wilkaniec, Magdalena Cieślik

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 528 - 528

Published: April 4, 2025

Neuroinflammation is a key feature of all neurodegenerative disorders, including Alzheimer’s disease, and tightly regulated by epigenetic mechanisms. Among them, bromodomain extraterminal domain (BET) proteins play crucial role recognizing acetylated histones acting as transcriptional co-regulators to modulate gene expression. This study investigates the potential inhibiting BET in preventing microglia-mediated neuronal damage vitro. Murine BV2 microglial cells were exposed lipopolysaccharide (LPS) or amyloid-β (Aβ) induce an inflammatory response, subsequent effects on murine HT22 examined. tested, only Brd4 was significantly upregulated upon pro-inflammatory stimulation. JQ1, potent pan-inhibitor proteins, suppressed LPS-induced upregulation cytokine mRNA levels, Il1b, Il6, Tnf, microglia. Pre-treatment with JQ1 attenuated cytotoxicity LPS-activated toward neurons. Additionally, conditioned media from Aβ fibril-stimulated induced cell death, which partially prevented pre-treatment JQ1. Co-culture assays further demonstrated beneficial effect inhibition. Our findings suggest that targeting may offer neuroprotective strategy modulating activation, potentially providing therapeutic benefits diseases.

Language: Английский

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