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Protein kinase C (PKC) activation induces cellular reprogramming and differentiation in various cell models. Although many effectors of PKC physiological actions have been elucidated, the molecular mechanisms regulating oligodendrocyte differentiation after PKC activation are still unclear. Here, we applied a liquid chromatography-mass spectrometry (LC-MS/MS) approach to provide a comprehensive analysis of the proteome expression changes in the MO3.13 oligodendroglial cell line after PKC activation. Our findings suggest that multiple networks that communicate and coordinate with each other may finally determine the fate of MO3.13 cells, thus identifying a modular and functional biological structure. In this work, we provide a detailed description of these networks and their participating components and interactions. Such assembly allows perturbing each module, thus describing its physiological significance in the differentiation program. We applied this approach by targeting the Rho-associated protein kinase (ROCK) in PKC-activated cells. Overall, our findings provide a resource for elucidating the PKC-mediated network modules that contribute to a more robust knowledge of the molecular dynamics leading to this cell fate transition.
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http://dx.doi.org/10.3390/ijms22105245 | DOI Listing |
Mol Divers
September 2025
Department of Biotechnology, National Institute of Technology Raipur, Raipur, Chhattisgarh, 492001, India.
Traditional drug discovery methods like high-throughput screening and molecular docking are slow and costly. This study introduces a machine learning framework to predict bioactivity (pIC₅₀) and identify key molecular properties and structural features for targeting Trypanothione reductase (TR), Protein kinase C theta (PKC-θ), and Cannabinoid receptor 1 (CB1) using data from the ChEMBL database. Molecular fingerprints, generated via PaDEL-Descriptor and RDKit, encoded structural features as binary vectors.
View Article and Find Full Text PDFInflammopharmacology
September 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA University), Giza, Egypt.
The neuroprotective potential of tyrosine kinase inhibitors (TKIs), potent anticancer drugs, was verified against various neurodegenerative insults, but not Huntington's disease (HD). These promising outcomes were due to their ability to modulate various intracellular signalling pathways. Hence, the current study aimed to evaluate the neuroprotective effects of lapatinib and pazopanib in the 3-nitropropionic (3-NP)-induced HD model in rats.
View Article and Find Full Text PDFAm J Forensic Med Pathol
September 2025
Department of Pathology, St Louis University School of Medicine, Office of the Medical Examiner - City of St. Louis, St. Louis, MO.
Myotonic dystrophy type 1, or dystrophia myotonica type 1 (DM1), is a multisystem disorder inherited in an autosomal dominant manner. It is caused by a CTG tri-nucleotide expansion in the 3'-untranslated region (3'-UTR) of the dystrophia myotonia protein kinase (DMPK) gene. Core clinical features include progressive skeletal muscle weakness, myotonia, and systemic complications, with premature mortality most often due to respiratory or cardiac dysfunction.
View Article and Find Full Text PDFJ Enzyme Inhib Med Chem
December 2025
Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, India.
The mitogen-activated protein kinase (MAPK) pathway-also known as the RAS/RAF/MEK/ERK pathway-is a critical signalling cascade involved in regulating cell growth, proliferation, and survival. First discovered in the early 1980s, the pathway's extracellular signal-regulated kinase (ERK) subfamily was identified in the 1990s. The ERK family includes several isoforms-ERK1, ERK2, ERK3, ERK5, and ERK6-with ERK1 (MAPK3) and ERK2 (MAPK1) being the most well-characterised and playing central roles in MAPK signalling.
View Article and Find Full Text PDFInt J Surg
September 2025
Department of Pediatric Dentistry, Faculty of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran.