L-Arginine inhibits NLRP3 inflammasome activation.

L-arginine directly binds the Asp31 site of NLRP3 and inhibits inflammasome assembly, blocking ASC interaction and activation in macrophages and mouse disease models.

• Why it matters: Nutritional and metabolic state are linked to inflammation, but the direct mechanism connecting diet-derived signals to NLRP3-driven inflammatory activation was unclear.
• What they did: The authors tested direct binding to NLRP3 at Asp31, then assessed how L-arginine supplementation versus deprivation altered NLRP3 activation in macrophages and in mice with monosodium urate crystal-induced arthritis, aluminium-induced peritonitis, and Parkinson’s disease models.
• The result: L-arginine supplementation inhibited NLRP3 activation and alleviated arthritis, peritonitis, and Parkinson’s neuroinflammation and motor deficits, while deprivation promoted pathology; in patients with Parkinson’s disease, serum L-arginine levels were reduced.

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