Published: Jan. 1, 2023
Language: Английский
MedComm, Journal Year: 2023, Volume and Issue: 4(3)
Published: May 29, 2023
Proteolysis targeting chimera (PROTAC) technology has become a powerful strategy in drug discovery, especially for undruggable targets/proteins. A typical PROTAC degrader consists of three components: small molecule that binds to target protein, an E3 ligase ligand (consisting and its recruiter), chemical linker hooks first two components together. In the past 20 years, we have witnessed advancement multiple degraders into clinical trials anticancer therapies. However, one major challenges is only very limited number recruiters are currently available as targeted protein degradation (TPD), although human genome encodes more than 600 ligases. Thus, there urgent need identify additional effective TPD applications. this review, summarized existing RING-type ubiquitin their act ligands application discovery. We believe review could serve reference future development efficient cancer discovery development.
Language: Английский
Citations
26
Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)
Published: Jan. 20, 2024
Abstract Background Alzheimer’s disease (AD) is a degenerative neurological disorder. Recent studies have indicated that histone deacetylases (HDACs) are among the most prominent epigenetic therapy targets and HDAC inhibitors therapeutic effects on AD. Here, we identified sodium valproate (VPA), pan-HDAC inhibitor, WT161, novel HDAC6 selective as potential agents for Underlying molecular mechanisms were investigated. Methods A cellular model, N2a-APPswe, was established via lentiviral infection, APPswe/PSEN1dE9 transgenic mouse model employed in study. LC–MS/MS applied to quantify concentration of WT161 brain. Western blotting, immunohistochemical staining, thioflavin-S staining ELISA detect protein expression cells, tissues, or serum. RNA interference utilized knockdown specific genes cells. The cognitive function mice assessed nest-building test, object recognition test Morris water maze test. Results Previous focused mainly impact deacetylase activity. Our study discovered VPA can downregulate multiple HDACs, such HDAC1 HDAC6, both AD cell models. Moreover, they also affect APP secretases (BACE1, PSEN1, ADAM10). subsequent vitamin C induction further confirmed indeed regulated by with JNK pathway being intermediate link this regulatory process. Through above pathways, effectively reduced Aβ deposition models significantly improved mice. Conclusions In general, HDAC6-JNK-APP cascade an important exert their Investigations into safety efficacy conducted, providing essential preclinical evidence assessing these two drugs treatment
Language: Английский
Citations
18
RSC Advances, Journal Year: 2025, Volume and Issue: 15(2), P. 966 - 1010
Published: Jan. 1, 2025
Benzimidazoles as anticancer epigenetic factors.
Language: Английский
Citations
2
Foods, Journal Year: 2025, Volume and Issue: 14(3), P. 347 - 347
Published: Jan. 21, 2025
Bee pollen is characterized by an exceptional diversity and abundance of micronutrients bioactive phytochemicals. This richness remains very sparsely investigated, but accumulating evidence strongly supports a promising future for bee in human nutrition medicine. Epigenetic regulation among the most compelling biomedical topics that remain completely untapped derivative research. In our current research, we identified numerous ubiquitous compounds are consistently present this matrix, regardless its botanical geographical origins, have been well studied documented as epigenetic regulators recent years. Given relative newness both research studies within nutritional, pharmaceutical, medical sciences, review aims to bridge these valuable fields advance related experimental investigations. To best knowledge, first work has aimed comprehensively investigate modulatory potential compounds. Our findings also unveiled several intriguing phenomena, such dual effect same compound depending on cellular context or some cross-generational heritability traits. Although whole extract still lacking, study clearly indicates avenue worth further We hope constitutes foundational cornerstone investigations
Language: Английский
Citations
2
Published: Jan. 3, 2024
A monolayer of endothelial cells (ECs) lines the lumen blood vessels and as such provides a semi-selective barrier between interstitial space. Compromise lung EC due to inflammatory or toxic events may results in pulmonary edema, which is cardinal feature acute injury (ALI) its more severe form, respiratory distress syndrome (ARDS). The functions are controlled, at least part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent largest group activated Zn2+. Members this HDAC involved regulation primarily modifying structure chromatin upon removal acetyl groups from histones. In addition, they can deacetylate many non-histone proteins, including those located extra nuclear compartments. Recently, therapeutic potential inhibiting zinc-dependent for preservation has gained momentum. However, role specific subtypes remains largely unknown. This review aims provide an update on dysfunction related diseases. We will broadly focus biological contributions, signaling pathways transcriptional roles pathobiology associated mainly with diseases we discuss their inhibitors prevention.
Language: Английский
Citations
5
Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12
Published: Jan. 16, 2024
Background: Patients with late-stage mild cognitive impairment (LMCI) have a higher risk of progression to Alzheimer’s disease (AD) than those early-stage (EMCI). However, previous studies often pooled EMCI and LMCI patients into single MCI group, limited independent investigation the pathogenesis LMCI. Methods: In this study, we employed whole-genome methylation association analysis determine differences in peripheral blood profiles between 663 aging (CN) 554 patients. Results: Our results revealed 2,333 differentially methylated probes (DMPs) 85 regions (DMRs) specific The top hit sites or were associated genes such as SNED1, histone deacetylases coding gene HDACs, HOX ZNF family. DNA methylations upregulated expression HDAC4, HDAC8, family HOXC5 HOXC9, but they downregulated ADCYAP1, ZNF415 ZNF502. Gene Ontology (GO) KEGG showed that these predominantly related processes addiction disorders, neurotransmission, neurogenesis. Out included 358 subjects (65%) had progressed AD. Further stable course (sLMCI) who AD (pLMCI) indicated signal intensities HDAC6, ZNF502, HOXC5, HOXC6, HOXD8 increased susceptibility Protective effects against noticed when SNED1 ZNF727 appeared Conclusion: findings highlight substantial number LMCI-specific biomarkers differ from identified case–control studies. These potential contribute better understanding
Language: Английский
Citations
5
Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 140 - 140
Published: Jan. 23, 2024
A monolayer of endothelial cells (ECs) lines the lumen blood vessels and, as such, provides a semi-selective barrier between and interstitial space. Compromise lung EC due to inflammatory or toxic events may result in pulmonary edema, which is cardinal feature acute injury (ALI) its more severe form, respiratory distress syndrome (ARDS). The functions are controlled, at least part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent largest group activated Zn2+. Members this HDAC involved regulation primarily modifying structure chromatin upon removal acetyl groups from histones. In addition, they can deacetylate many non-histone proteins, including those located extranuclear compartments. Recently, therapeutic potential inhibiting zinc-dependent for preservation has gained momentum. However, role specific subtypes remains largely unknown. This review aims provide an update on dysfunction related diseases. We will broadly focus biological contributions, signaling pathways transcriptional roles pathobiology associated mainly with diseases, we discuss their inhibitors prevention.
Language: Английский
Citations
5
Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(16), P. 13512 - 13533
Published: Aug. 2, 2024
In this Perspective, we have brought together available biological evidence on hydrazides as histone deacetylase inhibitors (HDACis) and a distinct type of Zn-binding group (ZBG) to be reviewed for the first time in literature. N-Alkyl transformed field, providing innovative practical chemical tools selective effective inhibition specific (HDAC) enzymes, addition usual hydroxamic acid o-aminoanilide ZBG-bearing HDACis. This has enabled efficient targeting neurodegenerative diseases such Alzheimer's disease, cancer, cardiovascular diseases, protozoal pathologies.
Language: Английский
Citations
5
Bioorganic & Medicinal Chemistry Letters, Journal Year: 2023, Volume and Issue: 81, P. 129148 - 129148
Published: Jan. 20, 2023
Language: Английский
Citations
10
Bioorganic & Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 102, P. 129670 - 129670
Published: Feb. 21, 2024
Language: Английский
Citations
4