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

и другие.

Biomolecules, Год журнала: 2025, Номер 15(4), С. 528 - 528

Опубликована: Апрель 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.

Язык: Английский

Epigenetic Mechanisms in the Transfer of Metabolic Disorders: A Comprehensive Review DOI Open Access

Swathi Nl,

Zaid Shakhatreh,

Ammar Tahir

и другие.

Cureus, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Epigenetic modifications, including deoxyribonucleic acid (DNA) methylation, histone and non-coding ribonucleic (ncRNAs), regulate gene expression without altering the DNA sequence play pivotal roles in pathogenesis of metabolic disorders (MDs), such as diabetes, obesity, cardiovascular diseases. This review aims to consolidate current knowledge on epigenetic mechanisms underlying MDs, emphasizing modifications ncRNAs. A comprehensive literature search was conducted using PubMed, Scopus, Web Science databases. Studies published between 2000 2024 (a few foundational historical articles were also added) screened terms "epigenetics AND disorders," "DNA methylation diabetes," "histone obesity," "non-coding RNA diseases." Relevant translational clinical studies reviewed synthesize existing evidence regulation Histone acetylation, phosphorylation, ubiquitination, contribute dysregulation by modulating chromatin accessibility transcription. Additionally, ncRNAs, microRNAs, long circular RNAs, influence pathways post-transcriptionally regulating key genes involved insulin resistance, lipid metabolism, inflammation. Emerging research highlights potential biomarkers for early disease detection prognosis, well therapeutic modulators, deacetylase inhibitors methylation-targeting agents. Despite promising advances, challenges remain translating findings into practice because inter-individual variability complex interplay genetics environmental factors. Future should focus large-scale, multicenter validate develop personalized interventions MDs.

Язык: Английский

Процитировано

0

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

и другие.

Biomolecules, Год журнала: 2025, Номер 15(4), С. 528 - 528

Опубликована: Апрель 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.

Язык: Английский

Процитировано

0