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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 (56) Simultaneously, the electrophilic properties of 4-HNE facilitate its formation of adducts with synaptic proteins (e.g., synapsin I, PSD-95), directly disrupting synaptic ultrastructure (194)