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Excess copper is reduced by FDX1 to generate Cu, which drives cell death via two primary mechanisms: (1) Cu-mediated aggregation of lipoylated TCA cycle proteins (e.g., DLAT) and loss of Fe-S clusters, and (2) Cu-induced disruption of the Npl4/p97 protein quality-control system

The significant increase in ENZ release with increasing GSH or DTT concentrations supports the disulfide bond cleavage mechanism

An invited commentary on this study, also published in JAMA Ophthalmology, challenges the idea that the increased risk of NAION among semaglutide users resulted directly from the medication

Semaglutide works by activating GLP-1 receptors in the brain and pancreas, slowing gastric emptying and reducing hunger signals

doi:10.1007/s12253-011-9404-9 91