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The P2X7 receptor (P2X7R), an ATP-gated ion channel, has emerged as a crucial player in neuroinflammation and a promising therapeutic target for neurodegenerative disorders. This review explores the current understanding of P2X7R's structure, activation, and physiological roles, focusing on its expression and function in microglial cells. The article examines the receptor's involvement in calcium signaling, microglial activation, and polarization, as well as its role in the pathogenesis of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. The review highlights the complex nature of P2X7R signaling, discussing its potential neuroprotective and neurotoxic effects depending on the disease stage and context. It also addresses the development of P2X7R antagonists and their progress in clinical trials, identifying key research gaps and future perspectives for P2X7R-targeted therapy development. By providing a comprehensive overview of the current state of knowledge and future directions, this review serves as a valuable resource for researchers and clinicians interested in exploring the therapeutic potential of targeting P2X7R for the treatment of neurodegenerative disorders.
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Introduction: The emerging concept of immunometabolism highlights the interplay between lipid metabolism and phagocytosis in macrophages. Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) has been identified as an essential modulator of both lipid metabolism and phagocytic function in macrophages. This study aims to investigate the roles of P53 and TREM2 in regulating macrophage lipid metabolism and phagocytosis and to evaluate the potential therapeutic effects of paeonol on these processes. Methods: CRISPR-Cas9 was utilized to generate P53 and TREM2 knockout RAW264.7 cell lines. The dual-luciferase reporter gene assay was performed to assess the interaction between P53 and the TREM2 promoter. A series of functional assays were conducted to evaluate the impact of P53 and TREM2 on macrophage lipid metabolism and phagocytic function. The effects of Paeonol on these processes were also examined. Results: Our findings revealed that paeonol induces the accumulation of P53 in the nucleus. P53 acts as a transcription factor that upregulates the expression of TREM2, promoting macrophage lipid metabolism, metabolic activity, and phagocytic capacity. Additionally, dual-luciferase reporter gene assays confirmed the interaction between P53 and the TREM2 promoter. Discussion: This study provides novel insights into the roles of P53 and TREM2 in regulating macrophage lipid metabolism and phagocytic function. Further research is warranted to explore the potential applications of Paeonol and to elucidate the molecular mechanisms underlying the observed effects.
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Myasthenia gravis is a major disease in the context of an ageing society, and the discovery of effective herbal compound and herbal active ingredients is a highly promising direction for the treatment of myasthenia gravis. In this study, we selected shujiao, dried ginger and ginseng from the compound ingredients through a network pathology approach. The three ingredients were used to obtain drug targets in Traditional Chinese Medicine Systems Pharmacology (TCMSP), HERB and BATMAN-TCM data and intersected with the disease targets of myasthenia gravis. The resulting regulatory network maps were then used to identify core genes through the String database, and finally the core genes were molecularly aligned with the corresponding active ingredients using Autodock vina software. The 'herbal-component-target' regulatory network of the Chinese herbal formulae was constructed, which is important for finding the potential molecular mechanism for the treatment of myasthenia gravis. It will provide a theoretical basis for the therapeutic and clinical research of myasthenia gravis.
