Repurposing the hypoglycaemic agents for neuroinflammation, a comprehensive review.

Abstract

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.