| IRAK1 (Interleukin-1 Receptor-Associated Kinase 1) — Serine/threonine kinase and key signaling mediator downstream of Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). Following MyD88-dependent receptor activation, IRAK4 activates IRAK1, which interacts with TRAF6 and promotes downstream TAK1, IKK/NF-κB, MAPK/JNK/p38, and inflammatory transcriptional signaling.
Typical modulation in cancer: Frequently ↑ or hyperactivated and generally tumor-promoting. Elevated IRAK1 signaling can support proliferation, survival, cancer stemness, inflammatory tumor microenvironment, migration, metastasis, and resistance to therapy. IRAK1 inhibition or degradation is therefore being investigated as an anticancer strategy.
Typical modulation in Alzheimer’s disease: ↑ IRAK1 signaling may contribute to TLR/IL-1-driven microglial and astrocytic neuroinflammation. Experimental inhibition of IRAK1/IRAK4 signaling has been investigated as a means of reducing neuroinflammatory signaling relevant to Alzheimer’s disease.
Typical mechanistic relationship: TLR / IL-1R → MyD88 → IRAK4 → IRAK1 → TRAF6 → TAK1 → NF-κB and MAPK activation ↑ → inflammatory cytokine expression ↑.
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