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the AGE-RAGE signaling, which induces axonal atrophy through p38 MAPK activation (Sango et al., 2025), and the PKC- activation, which impairs nerve blood flow via endothelin-1 overexpression ( Hyperglycemia-induced mitochondrial dysfunction in neuronal and Schwann cells leads to excessive O 2 production at complex I and III of the ETC, which initiates a cascade of injury through four primary mechanisms (Wu L