@misc{Matuszewska_Marta_Rola_2025,
 author={Matuszewska, Marta},
 editor={Czapski, Grzegorz A.},
 copyright={Creative Commons Attribution BY 4.0 license},
 address={Warszawa},
 howpublished={online},
 year={2025},
 publisher={Instytut Medycyny Doswiadczalnej i Klinicznej im. Miroslawa Mossakowskiego PAN},
 language={pol},
 abstract={Neurodegenerative diseases represent a major medical challenge due to their increasing prevalence and lack of effective therapies. Chronic neuroinflammation is a key component of their pathogenesis, in which excessive microglial activation leads to neuronal damage, synaptic dysfunction, and accumulation of pathological protein aggregates, including amyloid-β (Aβ) and hyperphosphorylated Tau. The limited efficacy of current anti- inflammatory strategies highlights the need for novel molecular targets, such as BET family proteins that regulate inflammatory gene expression. The aim of this study was to investigate the role of BET proteins in the regulation of microglial function and neuroinflammatory processes. Experiments were conducted using three models: in vitro (BV2 cells in mono- and co-culture with HT22, stimulated with LPS and Aβ), in vivo (C57BL/6J mice, endotoxemia model), and the maternal immune activation (MIA) model. Both pharmacological (JQ1, OTX-015) and genetic (siRNA) inhibition approaches were applied. Analyses included molecular biology, immunochemical, microscopy, cytometric methods, and behavioural tests. A selective increase in BRD4 expression was observed, indicating its central role in regulating pro-inflammatory gene expression, whereas BRD2 and BRD3 contribute to microglial homeostasis. BET inhibition reduced the expression of phagocytosis-related genes (CD33, TREM2), decreased phagocytic activity, and lowered pro-inflammatory cytokine levels (IL-1β, IL-6, TNF-α). It also attenuated microglia-induced neurotoxicity and reduced hippocampal Aβ levels without affecting Tau phosphorylation, while OTX-015 improved memory performance. These findings demonstrate that BET proteins are key regulators of microglial activity and represent promising therapeutic targets for neurodegenerative diseases, including Alzheimer’s disease.},
 title={Rola białek z rodziny BET w regulacji zależnych od komórek mikrogleju procesów neurodegeneracji},
 type={Text},
 URL={http://rcin.org.pl/imdik/Content/262352/Matuszewska_Marta_l.pdf},
 keywords={BET proteins, Microglia, Neuroinflammation, Neurodegenerative diseases},
}