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Despite extensive research, most therapeutic candidates fail to achieve sufficient CNS exposure due to the restrictive bloodbrain barrier (BBB), which blocks over 98% of small molecules and nearly all biologics from entering the brain parenchyma

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Additionally, curcumin stimulated the activation of MAPK pathway which in turn induced the expression of heterodimers of NF-E2-related factors 2 (Nrf2) that is responsible for ARE activation reporter genes [268]

In addition, Irg1-deficient phagocytes, which cannot produce itaconate, have shown increased susceptibility to M.tb infection, with infected mice exhibiting higher bacterial loads, reduced survival, exacerbated inflammation, extensive necrotizing granuloma formation and elevated neutrophil infiltration in the lungs [104, 105]