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A simplified scheme of the clock-NF-κB connection. BMAL1:CLOCK constitutes a loop controlled by PER:CRY heterodimers. Over them, RORα enhances BMAL1 and REV-ERBα represses it. Among other mechanisms, BMAL1 regulates nampt expression and the NAMPT protein that synthesizes NAD+, the cofactor for SIRT1. The deacetylase activity of SIRT1 inactivates NF-κB, controlling the immune response. When REV-ERBα dominates, blocks BMAL1 releasing the inflammatory activity of NF-κB
