RESUMEN
Mild cognitive impairment (MCI) is a neurodegenerative condition that is clinically prevalent among the elderly. EGB761 is widely recognized for its promising therapeutic properties in both the prevention and treatment of neurodegenerative disorders. The aim of this study was to investigate the effects of EGB761 in MCI and the underlying molecular mechanism. Four-month-old SAMP8 mice were used as an in vivo MCI model, and BV2 microglial cells were treated with ß-amyloid (Aß) 1-42 to establish an in vitro model. First, the cognitive function was evaluated by the Morris water maze. Then, Aß levels were measured by enzyme-linked immunosorbent assay. Finally, the underlying molecular mechanism was investigated both in vivo and in vitro. It was found that EGB761 treatment improved the cognitive impairment of SAMP8 mice. In addition, EGB761 inhibited NOD-like receptor protein 3 inflammasome-mediated pyroptosis-related mRNAs and proteins and reduced pyroptosis markers, including gasdermin D fluorescence intensity, propidium iodide-positive cell count, and the lactate dehydrogenase content. Furthermore, EGB761 inhibited extrinsic and intrinsic apoptosis. Thus, EGB761 had protective effects against pyroptosis and apoptosis in BV2 microglial cells induced by Aß1-42 and SAMP8 mice.
RESUMEN
The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key component of the innate immune system that triggers inflammation and pyroptosis and contributes to the development of several diseases. Therefore, blocking the activation of the NLRP3 inflammasome has therapeutic potential for the treatment of these diseases. MCC950, a selective small molecule inhibitor, has emerged as a promising candidate for blocking NLRP3 inflammasome activation. Ongoing research is focused on elucidating the specific targets of MCC950 as well as assessfing its metabolism and safety profile. This review discusses the diseases that have been studied in relation to MCC950, with a focus on stroke, Alzheimer's disease, liver injury, atherosclerosis, diabetes mellitus, and sepsis, using bibliometric analysis. It then summarizes the potential pharmacological targets of MCC950 and discusses its toxicity. Furthermore, it traces the progression from preclinical to clinical research for the treatment of these diseases. Overall, this review provides a solid foundation for the clinical therapeutic potential of MCC950 and offers insights for future research and therapeutic approaches.