Regulatory Role of NF-κB on HDAC2 and Tau Hyperphosphorylation in Diabetic Encephalopathy and the Therapeutic Potential of Luteolin DOI

Qian Fu,

Yilin Song,

Zhaoke Ling

et al.

Diabetes, Journal Year: 2024, Volume and Issue: 73(9), P. 1513 - 1526

Published: June 13, 2024

Diabetic encephalopathy (DE) is a severe complication of the central nervous system associated with diabetes. In this study, we investigated regulatory role mammalian target rapamycin (mTOR) on nuclear factor κB (NF-κB) in mice DE, and neuroprotective effect therapeutic mechanisms luteolin, natural flavonoid compound anti-inflammatory, antioxidant, properties. The results indicated that treatment luteolin improved degree cognitive impairment DE. It also decreased levels phosphorylated mTOR, NF-κB, histone deacetylase 2 (HDAC2) increased expression brain-derived neurotrophic synaptic-related proteins. Furthermore, protein-protein interaction Gene Ontology analysis revealed was involved network HDAC2 through mTOR/NF-κB signaling cascade. Our bioinformatics molecular docking may directly HDAC2, as an inhibitor, to alleviate complementing inhibition. Analysis luteolin's proteins their interactions suggest cognition. conclusion, tau hyperphosphorylation are regulated by cascade found reverse these effects, demonstrating its protective

Language: Английский

ZHX2 inhibits diabetes-induced liver injury and ferroptosis by epigenetic silence of YTHDF2 DOI Creative Commons
Wei Meng,

Linghua Li

Nutrition and Diabetes, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 22, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common complication of type 2 diabetes mellitus (DM). The transcription factor zinc fingers and homeoboxes (ZHX2) has been implicated in the pathogenesis chronic diseases, yet its precise role underlying mechanism DM-induced hepatic injury remain poorly elucidated. To investigate this, we used high-fat diet (HFD) streptozotocin (STZ) administration to create DM model mice, while high glucose (HG) exposure was simulate vitro. Through various experiments such as luciferase reporter assay, chromatin immunoprecipitation, RNA rescue experiments, aimed uncover mechanisms involving ZHX2. Our findings revealed that ZHX2 lower YTHDF2 higher livers mice HG-induced Huh7 cells. overexpression rescued injury. also reversed ferroptosis vivo Mechanistically, recognized m6A-modified mRNA promoted degradation. In turn, inhibited by binding promoter region. Knockdown led increased cells through activating YTHDF2-induced GPX4 SLC7A11 These highlight involvement ZHX2-YTHDF2-ferroptosis pathway suggest targeting this may hold therapeutic potential for improving injuries.

Language: Английский

Citations

0
Chemokine CX3CL1 (Fractalkine) Signaling and Diabetic Encephalopathy DOI Open Access
Mateusz Wątroba,

Anna D. Grabowska,

Dariusz Szukiewicz

et al.

Published: June 3, 2024

Diabetes mellitus (DM) is the most common metabolic disease in humans, and its prevalence increasing worldwide parallel with obesity pandemic. A lack of insulin or resistance, consequently hyperglycemia, leads to many systemic disorders, among which diabetic encephalopathy (DE) a long-term complication central nervous system (CNS), characterized by cognitive impairment motor dysfunctions. The role oxidative stress neuroinflammation pathomechanism DE has been proven. Fractalkine (CX3CL1) unique properties as an adhesion molecule chemoattractant, acting on only receptor, CX3CR1, it regulates activity microglia physiological states neuroinflammation. Depending clinical context, CX3CL1-CX3CR1 signaling may have neuroprotective effects inhibiting inflammatory process or, conversely, maintaining/intensifying inflammation neurotoxicity. This review discusses evidence supporting that pair other neurotoxic. Interrupting vicious cycle within neuron-microglia interactions be therapeutic goal limiting response.

Language: Английский

Citations

1
Chemokine CX3CL1 (Fractalkine) Signaling and Diabetic Encephalopathy DOI Open Access
Mateusz Wątroba,

Anna D. Grabowska,

Dariusz Szukiewicz

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7527 - 7527

Published: July 9, 2024

Diabetes mellitus (DM) is the most common metabolic disease in humans, and its prevalence increasing worldwide parallel with obesity pandemic. A lack of insulin or resistance, consequently hyperglycemia, leads to many systemic disorders, among which diabetic encephalopathy (DE) a long-term complication central nervous system (CNS), characterized by cognitive impairment motor dysfunctions. The role oxidative stress neuroinflammation pathomechanism DE has been proven. Fractalkine (CX3CL1) unique properties as an adhesion molecule chemoattractant, acting on only receptor, CX3CR1, it regulates activity microglia physiological states neuroinflammation. Depending clinical context, CX3CL1-CX3CR1 signaling may have neuroprotective effects inhibiting inflammatory process or, conversely, maintaining/intensifying inflammation neurotoxicity. This review discusses evidence supporting that pair other neurotoxic. Therefore, interrupting vicious cycle within neuron–microglia interactions promoting neurotoxic axis be therapeutic goal limiting response. However, optimal approach prevent simply tight glycemic control, because elimination dysglycemic CNS abolishes fundamental mechanisms induce this cycle.

Language: Английский

Citations

1
Regulatory Role of NF-κB on HDAC2 and Tau Hyperphosphorylation in Diabetic Encephalopathy and the Therapeutic Potential of Luteolin DOI

Qian Fu,

Yilin Song,

Zhaoke Ling

et al.

Diabetes, Journal Year: 2024, Volume and Issue: 73(9), P. 1513 - 1526

Published: June 13, 2024

Diabetic encephalopathy (DE) is a severe complication of the central nervous system associated with diabetes. In this study, we investigated regulatory role mammalian target rapamycin (mTOR) on nuclear factor κB (NF-κB) in mice DE, and neuroprotective effect therapeutic mechanisms luteolin, natural flavonoid compound anti-inflammatory, antioxidant, properties. The results indicated that treatment luteolin improved degree cognitive impairment DE. It also decreased levels phosphorylated mTOR, NF-κB, histone deacetylase 2 (HDAC2) increased expression brain-derived neurotrophic synaptic-related proteins. Furthermore, protein-protein interaction Gene Ontology analysis revealed was involved network HDAC2 through mTOR/NF-κB signaling cascade. Our bioinformatics molecular docking may directly HDAC2, as an inhibitor, to alleviate complementing inhibition. Analysis luteolin's proteins their interactions suggest cognition. conclusion, tau hyperphosphorylation are regulated by cascade found reverse these effects, demonstrating its protective

Language: Английский

Citations

0