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Targeting key signaling pathways associated with SR activationsuch as MAPK, NF-B, and JAK-STAThas been explored in clinical trials with mixed outcomes, largely due to SLE's intrinsic heterogeneity and overlapping immunopathogenic mechanisms (316, 372, 373)

Furthermore, research indicates that CPS1, the key enzyme in the urea cycle, is predominantly expressed in hepatocytes and certain renal cells, with low or absent expression in most immune cells due to the urea cycles inactivity in these cells (134, 135)

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Initially, activated M1 microglia drive the inflammatory response by secreting pro-inflammatory cytokines, which contribute to extracellular matrix degradation, disruption of cell integrity, and damage to the BBB [43]

10.1093/neuonc/nou358 73 OuR.LuS.WangL.WangY.LvM.LiT.et al (2022)