Inhibitor of Growth Proteins: Epigenetic Regulators Shaping Neurobiology

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 281 - 281

Published: Feb. 14, 2025

The inhibitor of growth (ING) family proteins is emerging as a pivotal regulator epigenetic modifications within the nervous system. These are involved in various cellular processes, including apoptosis, cell cycle control, and DNA repair, through interactions with chromatin-modifying complexes. Recent studies underscore dual role ING both tumor suppression neuronal differentiation, development, neuroprotection. This review summarizes functions neurobiology, focus on their involvement neural development relevance to neuro-oncological diseases. We explore mechanisms by which influence chromatin state gene expression, highlighting histone acetyltransferases, deacetylases, methyltransferases, modification enzymes, non-coding RNAs. A deeper understanding regulation system may pave way for novel therapeutic strategies targeting neurological disorders.

Language: Английский

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Growth arrest and DNA damage-inducible 45: a new player on inflammatory diseases

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 27, 2025

Growth arrest and DNA damage-inducible 45 (GADD45) proteins are critical stress sensors rapidly induced in response to genotoxic/physiological regulate many cellular functions. Even though the primary function of is block cell cycle, inhibit proliferation, promote apoptosis, repair damage cope with caused by internal external on body, evidence has shown that GADD45 also modulate innate adaptive immunity plays a broader role inflammatory autoimmune diseases. In this review, we focus immunomodulatory First, describe regulatory factors affect expression GADD45. Then, introduce its immunoregulatory roles immune cells signaling pathways mediated Finally, discuss effects various

Language: Английский

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Machine learning-based transcriptmics analysis reveals BMX, GRB10, and GADD45A as crucial biomarkers and therapeutic targets in sepsis

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 31, 2025

Sepsis is a life-threatening condition characterized by dysregulated host response to infection, resulting in high mortality rates and complex clinical management. This study leverages transcriptomics machine learning (ML) identify critical biomarkers therapeutic targets sepsis. Analyzing microarray data from the Gene Expression Omnibus (GEO) datasets GSE28750, GSE26440, GSE13205, GSE9960, we discovered three pivotal that BMX (bone marrow tyrosine kinase gene on chromosome X), GRB10 (growth factor receptor bound protein 10), GADD45A arrest DNA damage inducible alpha), exhibiting exceptional diagnostic accuracy (AUC >0.9). Functional enrichment analyses revealed these genes play key roles reactive oxygen species metabolism immune regulation. Specifically, was positively correlated with eosinophils inversely associated activated NK cells, CD8 T memory CD4 cells. showed positive correlations eosinophils, mast neutrophils, while linked M2 macrophages. Additionally, constructed comprehensive mRNA-miRNA-lncRNA regulatory network, identifying interactions may drive sepsis pathogenesis. Molecular docking dynamics simulations validated Bendroflumethiazide, Cianidanol, Hexamidine as promising agents targeting biomarkers. In conclusion, this integrated approach provides profound insights into molecular mechanisms underlying sepsis, pinpointing BMX, GRB10, targets. These findings significantly enhance our understanding of pathophysiology lay groundwork for developing personalized strategies aimed at improving patient outcomes.

Language: Английский

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XLOC_015548 Mitigates Skeletal Muscle Atrophy via the Gadd45g/MEK/ERK Pathway and Redox Regulation

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(4)

Published: April 22, 2025

Background: Skeletal muscle atrophy is a common musculoskeletal disorder that significantly reduces patient quality of life. Long non-coding RNA (lncRNA) XLOC_015548 has been identified as pivotal regulator C2C12 myoblast proliferation and differentiation. However, its role in mitigating denervation-induced the underlying mechanisms remain unclear. Methods: We employed lentiviral-mediated stable expression myoblasts skeletal muscle-specific XLOC_015548-edited mouse models to investigate function this lncRNA. Muscle were established vitro by glucocorticoid-induced with dexamethasone (DEX) vivo sciatic nerve transection-induced denervation. The MEK inhibitor U0126 was used assess growth arrest DNA damage-inducible 45 gamma/mitogen-activated protein kinase kinase/extracellular signal-regulated (Gadd45g/MEK/ERK) signaling pathway. Results: Overexpression activated MEK/ERK pathway (p < 0.05) downregulating Gadd45g promoting cytoplasmic localization, thereby enhancing cell myotube formation. Furthermore, reduced level reactive oxygen species (ROS) 0.01), stabilized mitochondrial membrane potential, alleviated DEX-induced oxidative stress. These protective effects partially reversed U0126, confirming involvement overexpression (q increased fiber cross-sectional area. Conclusion: plays critical myogenic differentiation protecting against regulating expression, activating pathway, reducing findings underscore therapeutic potential atrophy, provide foundation for lncRNA-based treatment strategies.

Language: Английский

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Semaglutide ameliorated autism-like behaviors and DNA repair efficiency in male BTBR mice by recovering DNA repair gene expression

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2024, Volume and Issue: 135, P. 111091 - 111091

Published: July 18, 2024

Language: Английский

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Salubrious effects of proanthocyanidins on behavioral phenotypes and DNA repair deficiency in the BTBR mouse model of autism

Saudi Pharmaceutical Journal, Journal Year: 2024, Volume and Issue: 32(11), P. 102187 - 102187

Published: Oct. 13, 2024

Autism is a neurodevelopmental disorder distinguished by impaired social interaction and repetitive behaviors. Global estimates indicate that autism affects approximately 1.6% of children, with the condition progressively becoming more prevalent over time. Despite noteworthy progress in research, remains untreatable. This serves as driving force for scientists to explore new approaches disease management. linked elevated levels oxidative stress disturbances DNA repair mechanism, which may potentially play role its comorbidities development. The current investigation aimed evaluate beneficial effect naturally occurring flavonoid proanthocyanidins on behavioral characteristics efficacy autistic BTBR mice. Moreover, mechanisms responsible these effects were clarified. present findings repeated administration effectively reduces altered behavior animals without altering motor function. Proanthocyanidins decreased strand breaks accelerated rate animals, evaluated modified comet test. In addition, reduced recovered disrupted mechanism decreasing expressions

Language: Английский

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