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Notably, 4-HNE can activate the PPAR pathway, suppressing PGC-1-mediated mitochondrial biogenesis and reducing local ATP supply at synapses, thereby impairing plasticity mechanisms such as LTP (194)

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This context-sensitivity is characteristic of compounds that interact with upstream transcriptional regulators rather than directly with NOS enzymatic activity

Though unlikely with typical product concentrations that fall within safe parameters, awareness of this risk remains important