Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 27, 2023

The ever-increasing prevalence of noncommunicable diseases (NCDs) represents a major public health burden worldwide. most common form NCD is metabolic diseases, which affect people all ages and usually manifest their pathobiology through life-threatening cardiovascular complications. A comprehensive understanding the will generate novel targets for improved therapies across spectrum. Protein posttranslational modification (PTM) an important term that refers to biochemical specific amino acid residues in target proteins, immensely increases functional diversity proteome. range PTMs includes phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, glycosylation, palmitoylation, myristoylation, prenylation, cholesterylation, glutathionylation, S-nitrosylation, sulfhydration, citrullination, ADP ribosylation, several PTMs. Here, we offer review roles pathological consequences, including diabetes, obesity, fatty liver hyperlipidemia, atherosclerosis. Building upon this framework, afford description proteins pathways involved by focusing on PTM-based protein modifications, showcase pharmaceutical intervention preclinical studies clinical trials, future perspectives. Fundamental research defining mechanisms whereby regulate open new avenues therapeutic intervention.

Язык: Английский

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Inflammatory Mediators of Endothelial Dysfunction

Life, Год журнала: 2023, Номер 13(6), С. 1420 - 1420

Опубликована: Июнь 20, 2023

Endothelial dysfunction (ED) is characterized by imbalanced vasodilation and vasoconstriction, elevated reactive oxygen species (ROS), inflammatory factors, as well deficiency of nitric oxide (NO) bioavailability. It has been reported that the maintenance endothelial cell integrity serves a significant role in human health disease due to involvement endothelium several processes, such regulation vascular tone, hemostasis thrombosis, adhesion, smooth muscle proliferation, inflammation. Inflammatory modulators/biomarkers, IL-1α, IL-1β, IL-6, IL-12, IL-15, IL-18, tumor necrosis factor α, or alternative anti-inflammatory cytokine IL-10, adhesion molecules (ICAM-1, VCAM-1), involved atherosclerosis progression have shown predict cardiovascular diseases. Furthermore, signaling pathways, NLRP3 inflammasome, are associated with response disrupted H2S bioavailability postulated be new indicators for inflammation its dysfunction. In this review, we summarize knowledge plethora reviews, research articles, clinical trials concerning key modulators pathways

Язык: Английский

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Hydrogen Sulfide: An Emerging Regulator of Oxidative Stress and Cellular Homeostasis—A Comprehensive One-Year Review

Antioxidants, Год журнала: 2023, Номер 12(9), С. 1737 - 1737

Опубликована: Сен. 7, 2023

Hydrogen sulfide (H2S), traditionally recognized as a toxic gas, has emerged critical regulator in many biological processes, including oxidative stress and cellular homeostasis. This review presents an exhaustive overview of the current understanding H2S its multifaceted role mammalian functioning management. We delve into sources function H2S, mechanisms underlying homeostasis, intricate relationships between these processes. explore evidence from recent experimental clinical studies, unraveling biochemical molecular dictating H2S’s roles modulating responses maintaining The implications therapeutic potential conditions characterized by dysregulation disrupted homeostasis are discussed, highlighting emerging significance health disease. Finally, this underscores challenges, controversies, future directions field, emphasizing need for further research to harness agent diseases associated with homeostatic imbalance. Through review, we aim emphasize pivotal function, encouraging exploration burgeoning area research.

Язык: Английский

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Hepatic Zbtb18 (Zinc Finger and BTB Domain Containing 18) alleviates hepatic steatohepatitis via FXR (Farnesoid X Receptor)

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Янв. 24, 2024

Abstract A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic liver disease (NAFLD), coupled with hepatitis insulin resistance. Yet the details of underlying mechanisms are not fully understood. Here, we unraveled that expression transcription factor Zbtb18 is markedly decreased in livers both patients murine models NAFLD. Hepatic knockout promoted NAFLD features like impaired energy expenditure oxidation (FAO), induced Conversely, hepatic overexpression alleviated hepato-steatosis, resistance, hyperglycemia mice fed on a high-fat diet (HFD) or diabetic mice. Notably, vitro vivo mechanistic studies revealed transcriptional activation Farnesoid X receptor ( FXR ) mediated FAO Clathrin Heavy Chain CLTC protein hinders NLRP3 inflammasome activity. This key mechanism by which hepatocyte’s alleviates consequent fibrosis was further verified FXR’ s deletion forced cultured mouse primary hepatocytes (MPHs). Moreover, significantly abrogated overexpression-driven inhibition activity macrophages. Altogether, transcriptionally activates -mediated expression, inhibits inflammasome’s alleviating inflammatory stress representing an attractive remedy for steatosis fibrosis.

Язык: Английский

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Unraveling hydrogen sulfide detection and lysosome-mitochondria fusion in mitophagy using dual phenothiazine-based fluorescence probes

Sensors and Actuators B Chemical, Год журнала: 2024, Номер 406, С. 135408 - 135408

Опубликована: Янв. 28, 2024

Язык: Английский

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Hydrogen sulfide donors across time: From origins to cutting-edge applications

Nitric Oxide, Год журнала: 2024, Номер 144, С. 29 - 39

Опубликована: Фев. 1, 2024

Язык: Английский

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Hydrogen sulfide regulates macrophage polarization and necroptosis to accelerate diabetic skin wound healing

International Immunopharmacology, Год журнала: 2024, Номер 132, С. 111990 - 111990

Опубликована: Апрель 3, 2024

Язык: Английский

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A Current Understanding of FXR in NAFLD: The multifaceted regulatory role of FXR and novel lead discovery for drug development

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 175, С. 116658 - 116658

Опубликована: Май 2, 2024

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has reached 30 %, with an annual increase. incidence NAFLD-induced cirrhosis is rapidly rising and become the leading indicator for transplantation in US. However, there are currently no US Food Drug Administration-approved drugs NAFLD. Increasing evidence underscores close association between NAFLD bile acid metabolism disorder, highlighting feasibility targeting signaling pathway treatment. farnesoid X receptor (FXR) endogenous acids that exhibits favorable effects ameliorating metabolic imbalance acids, lipid disorders, disruption intestinal homeostasis, all which key characteristics NAFLD, making FXR a promising therapeutic target present review provides comprehensive overview diverse mechanisms through improves particular emphasis on its involvement regulating homeostasis recent advancements drug development

Язык: Английский

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Insights on post-translational modifications in fatty liver and fibrosis progression

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер 1871(3), С. 167659 - 167659

Опубликована: Янв. 7, 2025

Язык: Английский

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Exogenous hydrogen sulfide improves non-alcoholic fatty liver disease by inhibiting endoplasmic reticulum stress/NLRP3 inflammasome pathway

Molecular and Cellular Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 8, 2025

Язык: Английский

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