SR-A3 suppresses AKT activation to protect against MAFLD by inhibiting XIAP-mediated PTEN degradation

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 11, 2025

Scavenger receptor class A member 3 (SR-A3) is implicated in metabolic diseases; however, the relationship between SR-A3 and dysfunction-associated fatty liver disease (MAFLD) has not been documented. Here, we show that hepatic expression significantly reduced human animal models context of MAFLD. Genetic inhibition hamsters elicits hyperlipidemia, hyperglycemia, insulin resistance, steatosis under chow-diet condition, yet escalates diet-induced Mechanistically, ablation enhances E3 ligase XIAP-mediated proteasomal ubiquitination PTEN, leading to AKT hyperactivation. By contrast, overexpression sufficient attenuate disorders WT fed a high-fat-high-cholesterol diet ob/ob mice via suppressing XIAP/PTEN/AKT axis. In parallel, pharmacological intervention by PTEN agonist oroxin B or lipid lowering agent ezetimibe differentially corrects MAFLD hamsters. diseases, but its with remains unclear. authors an important modulator energy metabolism potential therapeutic target against

Language: Английский

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Shared genetic architecture of COVID-19 and Alzheimer’s disease

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Oct. 20, 2023

The severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the сoronavirus disease 2019 (COVID-19) have become a global health threat. At height of pandemic, major efforts were focused on reducing COVID-19-associated morbidity mortality. Now is time to study long-term effects particularly cognitive impairment associated with long COVID. In recent years much attention has been paid possible relationship between COVID-19 Alzheimer’s disease, which considered main cause age-related impairment. Genetic predisposition was shown for both disease. However, analysis similarity genetic architecture these diseases usually limited indicating positive correlation them. this review, we described intrinsic linkages pointed out shared susceptibility genes that previously identified in genome-wide association studies highlighted panel SNPs includes candidate risk markers COVID-associated

Language: Английский

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Novel early-onset Alzheimer-associated genes influence risk through dysregulation of glutamate, immune activation, and intracell signaling pathways

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 5, 2024

Alzheimer Disease (AD) is a highly polygenic disease that presents with relatively earlier onset (≤70yo; EOAD) in about 5% of cases. Around 90% these EOAD cases remain unexplained by pathogenic mutations. Using data from and controls, we performed genome-wide association study (GWAS) trans-ancestry meta-analysis on non-Hispanic Whites (NHW, NCase=6,282, NControl=13,386), African Americans (AA NCase=782, NControl=3,663) East Asians (NCase=375, NControl=838 CO). We identified eight novel significant loci: six the ancestry-specific analyses two analysis. By integrating gene-based analysis, eQTL, pQTL functional annotations, nominate four genes are involved microglia activation, glutamate production, signaling pathways. These results indicate EOAD, although sharing many LOAD, harbors unique pathways could be used to create better prediction models or target identification for this type AD

Language: Английский

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Digestive System Diseases, Genetic Risk, and Incident Dementia: A Prospective Cohort Study

American Journal of Preventive Medicine, Journal Year: 2023, Volume and Issue: 66(3), P. 516 - 525

Published: Oct. 31, 2023

Language: Английский

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Integrin β3-Mediated Cell Senescence Associates with Gut Inflammation and Intestinal Degeneration in Models of Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5697 - 5697

Published: March 16, 2023

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by memory loss and personality changes that ultimately lead to dementia. Currently, 50 million people worldwide suffer from dementia related AD, the pathogenesis underlying AD pathology cognitive decline unknown. While primarily neurological of brain, individuals with often experience intestinal disorders, gut abnormalities have been implicated as major risk factor in development relevant However, mechanisms mediate injury contribute vicious cycle between brain remain In present study, bioinformatics analysis was performed on proteomics data variously aged mouse colon tissues. We found levels integrin β3 β-galactosidase (β-gal), two markers cellular senescence, increased age colonic tissue mice AD. The advanced artificial intelligence (AI)-based prediction also demonstrated association β-gal phenotypes. Moreover, we showed elevated were accompanied senescence phenotypes immune cell accumulation tissue. Further, genetic downregulation abolished upregulated inflammatory responses epithelial cells conditions associated provide new understanding molecular actions underpinning during suggest may function novel target mediating this disease.

Language: Английский

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