Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders DOI Creative Commons
Elena Rita Simula, Seyedesomaye Jasemi, Davide Cossu

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 415 - 415

Published: April 15, 2025

Human Endogenous Retroviruses comprise approximately 8% of the human genome, serving as fragments ancient retroviral infections. Although they are generally maintained in a silenced state by robust epigenetic mechanisms, specific HERV groups, particularly HERV-W and HERV-K, can become derepressed under pathological conditions, thereby contributing to initiation progression neuroinflammatory neurodegenerative processes. Preclinical studies clinical trials, such those investigating monoclonal antibodies, indicate that directly targeting these elements may offer novel therapeutic strategy. In this review, we provide an overview HERVs′ biology, examine their role diseases amyotrophic lateral sclerosis, multiple Alzheimer′s disease, Parkinson′s explore prospects, highlighting both challenges potential future research directions needed translate approaches into interventions.

Language: Английский

Oxidative-Stress-Mediated Epigenetic Dysregulation in Spermatogenesis: Implications for Male Infertility and Offspring Health DOI Open Access
Aris Kaltsas,

Eleftheria Markou,

Maria-Anna Kyrgiafini

et al.

Genes, Journal Year: 2025, Volume and Issue: 16(1), P. 93 - 93

Published: Jan. 17, 2025

Male reproductive health is governed by an intricate interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms—encompassing DNA methylation, histone modifications, non-coding RNA activity—are crucial both for spermatogenesis sperm maturation. However, oxidative stress, driven excessive reactive oxygen species, disrupts these processes, leading to impaired function male infertility. This disruption extends epigenetic resulting in abnormal gene expression chromatin remodeling that compromise genomic integrity fertilization potential. Importantly, oxidative-stress-induced alterations can be inherited, affecting the fertility offspring future generations. review investigates how stress influences regulation reproduction modifying RNAs, ultimately compromising spermatogenesis. Additionally, it discusses transgenerational implications disruptions their potential role hereditary infertility disease predisposition. Understanding mechanisms vital developing therapeutic strategies mitigate damage restore homeostasis germline. By integrating insights from molecular, clinical, research, this work emphasizes need targeted interventions enhance prevent adverse outcomes progeny. Furthermore, elucidating dose–response relationships between changes remains a critical research priority, informing personalized diagnostics interventions. In context, studies should adopt standardized markers damage, robust clinical trials, multi-omic approaches capture complexity Such rigorous investigations will reduce risk disorders optimize outcomes.

Language: Английский

Citations

3
The class-IIa HDAC inhibitor TMP269 promotes BMP-Smad signalling and is neuroprotective in in vitro and in vivo 6-hydroxydopamine models of Parkinson’s disease. DOI Creative Commons
Alexander T. O’Mahony, Martina Mazzocchi,

Alex Morris

et al.

Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110319 - 110319

Published: Jan. 1, 2025

Language: Английский

Citations

1
Epigenetics in autoimmune diseases: Unraveling the hidden regulators of immune dysregulation DOI Creative Commons
Giacomo Bagni, Edoardo Biancalana,

Emanuele Chiara

et al.

Autoimmunity Reviews, Journal Year: 2025, Volume and Issue: 24(6), P. 103784 - 103784

Published: March 3, 2025

Autoimmune diseases result from complex interactions between genetic and environmental factors. Recent advances in epigenetic research shed light on the intricate regulatory mechanisms that contribute to development progression of such conditions. The present review aims explore role modifications, including DNA methylation, histone non-coding RNAs, context autoimmune diseases. We discuss current understanding alterations associated with various disorders, their impact immune cell function, potential as innovative therapeutic targets. Additionally, we highlight main future directions field epigenetics autoimmunity.

Language: Английский

Citations

1
Bridging epigenomics and tumor immunometabolism: molecular mechanisms and therapeutic implications DOI Creative Commons
Xiaowen Xie, Weici Liu, Zhiyuan Yuan

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 8, 2025

Epigenomic modifications—such as DNA methylation, histone acetylation, and methylation—and their implications in tumorigenesis, progression, treatment have emerged a pivotal field cancer research. Tumors undergo metabolic reprogramming to sustain proliferation metastasis nutrient-deficient conditions, while suppressing anti-tumor immunity the tumor microenvironment (TME). Concurrently, immune cells within immunosuppressive TME adaptations, leading alterations function. The complicated interplay between metabolites epigenomic modulation has spotlighted significance of regulation immunometabolism. In this review, characteristics modification associated with tumors are systematically summarized alongside regulatory roles Classical emerging approaches delineated broaden boundaries research on crosstalk immunometabolism epigenomics. Furthermore, we discuss potential therapeutic strategies that target modulate modifications, highlighting burgeoning synergy therapies immunotherapy promising avenue for treatment.

Language: Английский

Citations

1
Epigenetic Regulation of Stromal and Immune Cells and Therapeutic Targets in the Tumor Microenvironment DOI Creative Commons
Kang Liu, Yue Li, Minmin Shen

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 71 - 71

Published: Jan. 6, 2025

The tumor microenvironment (TME) plays a pivotal role in neoplastic initiation and progression. Epigenetic machinery, governing the expression of core oncogenes suppressor genes transformed cells, significantly contributes to development at both primary distant sites. Recent studies have illuminated how epigenetic mechanisms integrate external cues downstream signals, altering phenotype stromal cells immune cells. This remolds area surrounding ultimately fostering an immunosuppressive microenvironment. Therefore, correcting TME by targeting modifications holds substantial promise for cancer treatment. review synthesizes recent research that elucidates impact specific regulations-ranging from DNA methylation histone chromatin remodeling-on within TME. Notably, we highlight their functional roles either promoting or restricting We also discuss potential applications agents treatment, envisaging ability normalize ecosystem. aims assist researchers understanding dynamic interplay between epigenetics TME, paving way better therapy.

Language: Английский

Citations

0
c-FLIP/Ku70 complex; A potential molecular target for apoptosis induction in hepatocellular carcinoma DOI

Yasamin Haghir-Sharif-Zamini,

Arezoo Khosravi, Moustapha Hassan

et al.

Archives of Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown, P. 110306 - 110306

Published: Jan. 1, 2025

Language: Английский

Citations

0
Exploring viral mimicry combined with epigenetics and tumor immunity: new perspectives in cancer therapy DOI Creative Commons
Ruirui Wang, Xin Dong,

Xiongjian Zhang

et al.

International Journal of Biological Sciences, Journal Year: 2025, Volume and Issue: 21(3), P. 958 - 973

Published: Jan. 6, 2025

Viral mimicry refers to an active antiviral response triggered by the activation of endogenous retroviruses (ERVs), usually manifested formation double-stranded RNA (dsRNA) and cellular interferon response, which activates immune system produces anti-tumor effects. Epigenetic studies have shown that epigenetic modifications (e.g. DNA methylation, histone modifications, etc.) play a crucial role in tumorigenesis, progression, treatment resistance. Particularly, alterations methylation may be closely associated with suppression ERVs expression, demethylation restore activity thus strengthen tumor response. Therefore, we propose viral can induce responses microenvironment activating expression ERVs, key regulatory this process. In paper, review intersection mimicry, epigenetics immunotherapy, explore possible interactions synergistic effects among three, aiming provide new theoretical basis potential strategies for cancer immunotherapy.

Language: Английский

Citations

0
Epigenomic Echoes—Decoding Genomic and Epigenetic Instability to Distinguish Lung Cancer Types and Predict Relapse DOI Creative Commons
Anke Baumann, Zholdas Buribayev, Olaf Wolkenhauer

et al.

Epigenomes, Journal Year: 2025, Volume and Issue: 9(1), P. 5 - 5

Published: Feb. 5, 2025

Genomic and epigenomic instability are defining features of cancer, driving tumor progression, heterogeneity, therapeutic resistance. Central to this process epigenetic echoes, persistent dynamic modifications in DNA methylation, histone modifications, non-coding RNA regulation, chromatin remodeling that mirror underlying genomic chaos actively influence cancer cell behavior. This review delves into the complex relationship between these illustrating how they collectively shape genome, affect repair mechanisms, contribute evolution. However, dynamic, context-dependent nature changes presents scientific ethical challenges, particularly concerning privacy clinical applicability. Focusing on lung we examine specific patterns function as biomarkers for distinguishing subtypes monitoring disease progression relapse.

Language: Английский

Citations

0
AI-assisted protein design to rapidly convert antibody sequences to intrabodies targeting diverse peptides and histone modifications DOI Creative Commons
Gabriel Galindo,

Daiki Maejima,

Jacob DeRoo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

ABSTRACT Intrabodies are engineered antibodies that function inside living cells, enabling therapeutic, diagnostic, and imaging applications. While powerful, their development has been hindered by challenges associated with folding, solubility, stability in the reduced intracellular environment. Here, we present an AI-driven pipeline integrating AlphaFold2, ProteinMPNN, live-cell screening to optimize antibody framework regions while preserving epitope-binding complementarity-determining regions. Using this approach, successfully converted 19 out of 26 sequences into functional single-chain variable fragment (scFv) intrabodies, including a panel targeting diverse histone modifications for real-time chromatin dynamics gene regulation. Notably, 18 these had failed convert using standard demonstrating unique effectiveness our method. As sequence databases expand, method will accelerate intrabody design, making easier, more cost-effective, broadly accessible biological research.

Language: Английский

Citations

0
Novel Epigenetics Control (EpC) Nanocarrier for Cancer Therapy Through Dual-Targeting Approach to DNA Methyltransferase and Ten-Eleven Translocation Enzymes DOI Creative Commons

R. Mitsuhashi,

Kiyoshi Sato, Hiroyoshi Kawakami

et al.

Epigenomes, Journal Year: 2025, Volume and Issue: 9(1), P. 6 - 6

Published: Feb. 11, 2025

Aberrant hypermethylation in the promoter regions of tumor suppressor genes facilitates pathogenesis and progression cancer. Therefore, inhibitors targeting DNA methyltransferase (DNMT) have been tested clinical studies. However, current monotherapy DNMT shows limited efficacy. Furthermore, mechanism action is replication-dependent. To address these limitations, we developed a novel core-shell-type "epigenetics control (EpC) nanocarrier" that encapsulated decitabine (5-aza-dC) PLGA core nanoparticle hybridized TET1 gene-encoding pDNA on lipid shell surface. This study aimed to evaluate whether dual delivery could synergistically enhance gene expression induce cell cycle arrest and/or apoptosis cancer cells. Herein, demonstrate potential EpC carrier HCT116 human colon cells upregulate rapidly achieve arrest. nanoparticles were prepared by W/O/W double emulsion method. The formation core-shell complexation with investigated optimized dynamic light scattering, zeta measurement, agarose gel electrophoresis. cellular uptake transfection efficiency measured confocal laser scanning microscopy luciferase assay, respectively. p53 protein was detected Western blotting. anti-tumor effects nanocarrier evaluated analysis an assay. delivered inhibitor TET into It promoted induced rapid G2/M phase Our findings suggest dual-targeting enzymes effectively repairs aberrant methylation induces growth cells, strategy may contribute advancement epigenetic therapy.

Language: Английский

Citations

0