The Protective Effects of TLR2/NOD2 Combined Agonist CL429 on 14.1 MeV Neutron-Radiation Damage.

High-energy neutron radiation (HENR) induces severe cellular and tissue damage, yet effective prophylactic agents remain limited. In this study, the TLR2/NOD2 co-agonist CL429 was evaluated for its radioprotective potential against 14.1 MeV neutron exposure. A murine HENR model was established, and absorbed doses were calculated using the specific kinetic energy method. Pretreatment with CL429 significantly improved survival outcomes, with survival rates reaching 90% and prolonged survival times observed. CL429 administration markedly increased the organ indices of the spleen, thymus, and testis, reduced splenocyte apoptosis to near-normal levels, and restored leukocyte and platelet counts in the early postirradiation phase. Flow cytometry and Western blot analyses indicated that CL429 upregulated TLR2 and NOD2 expression, accompanied by activation of downstream signaling pathways. These findings suggest that CL429 confers significant protection against neutron radiation-induced injury, potentially through the dual activation of TLR2/NOD2-mediated protective mechanisms.