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Neuronal nitric oxide synthase and inducible nitric oxide synthase are two distinct isoforms within the nitric oxide synthase family of enzymes that catalyze the production of nitric oxide (NO) from L-arginine. nNOS is constitutively expressed in neurons (but also found in other tissues such as skeletal muscle and vascular endothelium), where it regulates synaptic transmission, neurogenesis, learning, memory, and blood pressure. iNOS is typically undetectable but is strongly induced by inflammatory stimuli, particularly in immune cells such as macrophages, and generates high, sustained levels of NO as part of the innate immune response. Both isoforms are targets for drug discovery in a range of diseases including neurodegeneration, inflammation, cardiovascular disorders, and cancer. However, selective targeting is required to avoid side effects due to the diverse and critical physiological roles of NO signaling across tissues[1][3][4][6].
Competitive inhibition of substrate (L-arginine) binding Blockade of cofactor (tetrahydrobiopterin, BH4) utilization Inhibition of dimerization or calmodulin binding Downregulation of gene transcription (for iNOS inhibition in immune settings)
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