Most of the pyroptosis inhibitors targeted Gasdermin D (GSDMD) are functioning by restraining GSDMD-N (p30) oligomerization. For the first time, this work discovered a pyroptosis inhibitor taking effect by degrading p30 and GSDMD. As the principal bioactive constituent in Erigeron breviscapus, scutellarin (SCU) assumes a pivotal role in the realm of anti-inflammatory processes. In this study, SCU demonstrated efficacy in hindering pyroptosis mediated by the NOD-like receptor protein 3 (NLRP3) inflammasome, absent in melanoma 2 (AIM2) inflammasome, NLR-family CARD-containing protein 4 (NLRC4) inflammasome, and that activated through the non-canonical pathway. The inhibitory effect is achieved by thwarting apoptosis-associated speck-like protein containing CARD (ASC) oligomerization and inducing the ubiquitin-dependent selective autophagy of p30/GSDMD. Throughout the autophagic process, SCU facilitates selective autophagy of the pyroptosis executor p30/GSDMD through K33-linked polyubiquitination at Lys51 catalyzed by the E3 ligase tripartite motif-containing 21 (TRIM21). This process contributes to the recognition of p30/GSDMD by the cargo receptor sequestosome 1 (SQSTM1)/p62. The characteristic positions SCU as a prospective clinical intervention for a broader spectrum of inflammatory-related disorders.
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http://dx.doi.org/10.1016/j.phrs.2025.107605 | DOI Listing |
J Cardiovasc Transl Res
January 2025
Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, China.
Myocardial ischemia/reperfusion (I/R)-induced cell death, such as autophagy and ferroptosis, is a major contributor to cardiac injury. Regulating cell death may be key to mitigating myocardial ischemia/reperfusion injury (MI/RI). Autophagy is a crucial physiological process involving cellular self-digestion and compensation, responsible for degrading excess or malfunctioning long-lived proteins and organelles.
View Article and Find Full Text PDFNeurobiol Dis
January 2025
Department of Neurology and Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Southern Research, Birmingham, AL 35205, USA. Electronic address:
Mitochondrial dysfunction, transcriptional dysregulation, and protein aggregation are hallmarks of multiple neurodegenerative disorders, including Huntington's disease (HD). Strategies are needed to counteract these processes to restore neuronal health and function in HD. Recent evidence indicates that the transcription factor estrogen-related receptor gamma (ERRγ/Esrrg) is required for normal expression of mitochondrial, synaptic, and autophagy genes in neurons.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Biol Lipids
January 2025
Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha 410013, China. Electronic address:
Background: The phenotypic switch of vascular smooth muscle cells (VSMCs) underlies the pathology of many cardiovascular diseases. Histone deacetylase 3 (HDAC3) is reported to upregulate in several cardiovascular diseases. RGFP966 is a highly selective HDAC3 inhibitor.
View Article and Find Full Text PDFLupus
January 2025
Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Background: Systemic lupus erythematosus is a common autoimmune disease. Studies have suggested that defective stem cells could be involved in the pathogenesis of systemic lupus erythematosus, which leads to changes in the function of immune cells. By observing the cell morphology, autophagy, and senescence of bone marrow mesenchymal stem cells (BMSCs) from lupus mice and normal controls, this study investigated the role of IL-6 in autophagy and senescence of BMSCs and explored relevant mechanisms.
View Article and Find Full Text PDFFront Microbiol
January 2025
College of Forestry and Prataculture, Ningxia University, Yinchuan, China.
Introduction: strain NQ8GII4 is an endophytic fungus with significant potential for improving growth and disease resistance of alfalfa. However, the molecular mechanisms underlying the symbiotic relationship between NQ8GII4 and alfalfa roots remain poorly understood.
Methods: In this study, we conducted (1) a comparative genomic analysis of selected saprophytic, pathogenic, and endophytic fungi, including molecular phylogeny analysis, whole-genome alignment, and divergence date estimation positioning, and (2) transcriptomic profiling of alfalfa roots infected with NQ8GII4.
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