β-alanine alleviates gout by inhibiting NLRP3 inflammasome activation

Abstract The NLRP3 inflammasome plays a pivotal role in mediating pro-inflammatory cytokine release and inducing pyroptosis. Its aberrant activation is implicated in various inflammatory diseases, including gout, a condition characterized by monosodium urate crystal deposition in the ankle joint. Here, we identify β-alanine, an endogenous amino acid, as a novel NLRP3 inflammasome inhibitor with promising therapeutic potential for gout. Mechanistic investigations reveal that β-alanine binds to NLRP3, sequestering it within the trans-Golgi network. This interaction disrupts NLRP3 inflammasome assembly, thereby inhibiting the secretion of interleukin-1β (IL-1β) and IL-18. Moreover, in vivo experiments demonstrate that β-alanine administration significantly alleviates monosodium urate crystal-induced inflammation and joint swelling in mice without evident toxicity. Collectively, our findings not only uncover a novel endogenous regulatory mechanism for NLRP3-driven inflammation but also position β-alanine as a potential therapeutic candidate for gout.