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Inhibition of IRE-1α Alleviates Pyroptosis and Metabolic Dysfunction-Associated Steatohepatitis by Suppressing Gasdermin D.
Liver Int
February 2025
Department of Liver Transplantation Center and National Health Commission (NHC) Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China.
Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for cirrhosis and hepatocellular carcinoma, for which there is currently no effective treatment. This study aimed to investigate the regulatory mechanism between endoplasmic reticulum stress (ER stress) and pyroptosis in the liver under the context of MASH.
Methods And Results: Pyroptosis was examined in both in vivo and in vitro ER stress models.
Examining the potential involvement of NONO in TDP-43 proteinopathy in Drosophila.
Eur J Neurosci
January 2025
Department of Genetics and Evolution and Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, Geneva, Switzerland.
The misfolding and aggregation of TAR DNA binding protein-43 (TDP-43), leading to the formation of cytoplasmic inclusions, emerge as a key pathological feature in a spectrum of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). TDP-43 shuttles between the nucleus and cytoplasm but forms nuclear bodies (NBs) in response to stress. These NBs partially colocalise with nuclear speckles and paraspeckles that sequester RNAs and proteins, thereby regulating many cellular functions.
View Article and Find Full Text PDFPleiotrophin Prevents HO-Induced Senescence of Dental Pulp Stem Cells.
J Oral Rehabil
December 2024
Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing, China.
Background: Dental pulp stem cells (DPSCs) are widely used in research on dental tissue regeneration and systemic disease treatment. However, the oxidative microenvironment often causes cellular senescence, leading to decreased function. Our previous study demonstrated that pleiotrophin (PTN), a secreted extracellular matrix-associated protein, could rescue the proliferative capacity and osteogenic differentiation of replicative senescent DPSCs.
View Article and Find Full Text PDFSARS-CoV-2 N protein recruits G3BP to double membrane vesicles to promote translation of viral mRNAs.
Nat Commun
December 2024
Division of Virology and Immunology, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Ras-GTPase-activating protein SH3-domain-binding proteins (G3BP) are critical for the formation of stress granules (SGs) through their RNA- and ribosome-binding properties. SARS-CoV-2 nucleocapsid (N) protein exhibits strong binding affinity for G3BP and inhibits infection-induced SG formation soon after infection. To study the impact of the G3BP-N interaction on viral replication and pathogenesis in detail, we generated a mutant SARS-CoV-2 (RATA) that specifically lacks the G3BP-binding motif in the N protein.
View Article and Find Full Text PDFCytoplasmic Aggregates of Splicing Factor Proline-Glutamine Rich Disrupt Nucleocytoplasmic Transport and Induce Persistent Stress Granules.
J Cell Mol Med
December 2024
Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Splicing factor proline-glutamine rich (SFPQ), a multifunctional RNA-binding protein (RBP), shows cytoplasmic colocalisation with stress granule (SG) markers; however, the causative relationship and mechanism underlying this coalescence of SFPQ aggregates and SGs remain unclear. In this study, we demonstrate that SFPQ lacking its nuclear localisation sequence spontaneously forms cytoplasmic aggregates that abnormally incorporate immature RNA and induce persistent SGs. mRNA profiling showed that SFPQ mislocalisation induced extensive changes in RNA processing, with a subset of alternatively spliced transcripts associated with nucleocytoplasmic transport.
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