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The shared pathways between neuroinflammation and diabetes mellitus involve the NLRP3 inflammasome and subsequent production of the IL-1β. Chronic hyperactivation of hypothalamo-pituitary-adrenal axis and innate immunity are implicated in neurological disorders and diabetes. Repurposing drugs with anti-inflammatory properties allows for faster clinical translation in neuroinflammation as compared to developing new drugs from scratch. Few repurposed drugs have already undergone safety and efficacy testing for other conditions, making them attractive candidates for the neuroinflammatory disorders. Gliburide, an oral hypoglycaemic effectively inhibits the NLRP3 inflammasome, signifying that it may be used to treat the neuroinflammation-related disorders. A GLP-1 receptor agonist, liraglutide established encouraging effects in regulating hyperglycaemia and possibly lowering neuroinflammation. Patients who were obese and receiving liraglutide saw improvements in their glycaemic control and a decrease in neuroinflammatory markers in addition to the weight loss. Studies on mice suggested that, sulphonyl-ureas have properties to decrease the neuroinflammatory conditions and has potential benefits by targeting the NLRP3 inflammasome pathway, modulating lipopolysaccharide induced micro and astroglial neuroinflammation by activating the ERK/STAT3/NF-κB signalling pathways. Empagliflozin offered neuroprotection and helped in neurovascular remodelling, which is crucial for maintaining cognitive function. Repurposing is already-approved for the antidiabetic medications, such as insulin, metformin and thiazolidinediones. Insulin may be a viable and effective approach to treat neuroinflammation. In conclusion, the interplay between diabetes and neuroinflammation highlights the importance of metabolic health in neurodegenerative diseases. Understanding these shared pathways can inform strategies for prevention and treatment, potentially targeting both conditions simultaneously.
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http://dx.doi.org/10.1007/s13205-025-04455-7 | DOI Listing |
Ageing Res Rev
September 2025
Department of Neurology, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA. Electronic address:
Perioperative neurocognitive disorders (PNDs) are common complications following surgery, especially in elderly patients, and are characterized by memory loss, attention deficits, and impaired executive function. The pathogenesis of PNDs involves a complex interplay of neuroinflammation, neurotransmitter imbalance, epigenetic modifications, and gut-brain axis disruption. This review summarizes the latest findings on the mechanisms underlying PNDs, with a focus on microglial activation, interleukin imbalance, and NLRP3 inflammasome-mediated pyroptosis.
View Article and Find Full Text PDFInt J Biochem Cell Biol
September 2025
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. Electronic address:
Silicosis is a fatal occupational lung disease characterized by persistent inflammation and irreversible fibrosis. However, the pathogenesis of silicosis is currently unclear. In this study, a mouse model of silicosis was established by intranasal instillation of silica, and transcriptomic alterations in lung tissues were assessed by mRNA-sequencing.
View Article and Find Full Text PDFToxicon
September 2025
Department of Pathology, College of Medicine, King Khalid University, P.O. 641, Abha, 61421, Saudi Arabia; Department of Forensic Medicine and Clinical Toxicology, Mansoura University, Egypt.
Titanium dioxide nanoparticles (TiO-NPs) are used in the production of various industrial and commercial products and reported to cause neurotoxicity in Sprague Dawley rats. Fortunellin (FRN) is a potent flavonoid with diverse biological properties. This research experiment was performed to explore the protective role FRN against TiO-NPs induced brain damage.
View Article and Find Full Text PDFInt Immunopharmacol
September 2025
Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325000, China.
Peripheral nerve injury (PNI) is notoriously difficult to repair due to impaired axonal regeneration and dysregulated inflammatory microenvironments. This study demonstrates that crocin facilitates peripheral nerve regeneration by modulating the STAT3/Bcl-2/Beclin-1 signaling axis, enhancing autophagy while suppressing NLRP3 inflammasome-mediated pyroptosis. In a rat model of sciatic nerve crush injury, crocin treatment improved axonal regrowth and ultrastructural remyelination, as evidenced by upregulated expression of β3-Tubulin, neurofilament-200 (NF200), and myelin basic protein (MBP), alongside significantly elevated sciatic functional index (SFI) scores, reduced muscle atrophy, and diminished collagen deposition.
View Article and Find Full Text PDFNat Immunol
September 2025
Department of Microbiology, University of Chicago, Chicago, IL, USA.
Cholesterol-dependent cytolysins (CDCs) constitute the largest group of pore-forming toxins and serve as critical virulence factors for diverse pathogenic bacteria. Several CDCs are known to activate the NLRP3 inflammasome, although the mechanisms are unclear. Here we discovered that multiple CDCs, which we referred to as type A CDCs, were internalized and translocated to the trans-Golgi network (TGN) to remodel it into a platform for NLRP3 activation through a unique peeling membrane mechanism.
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