Proteomic Investigation of Neurotrophic trans-Banglene Reveals Potential Link to Iron Homeostasis

In an effort to gain insight into cellular systems impacted by neurotrophic trans-banglene (t-BG), global proteomic profiling and Western blot analyses were employed. Expression level changes in response to t-BG treatment were compared to those observed with nerve growth factor (NGF), a natural neurotrophic protein and functional analog to t-BG. Findings from these studies did not point to direct interception of NGF/TrkA signaling by t-BG. Instead, significant alterations in iron-binding and iron-regulating proteins were observed. While total iron levels showed no change across all treatments, intracellular iron measurements and mitochondrial iron measurements demonstrated lower ferrous (Fe²⁺) ion levels in t-BG treated cells but not in NGF treated cells. These results highlight a potential connection between iron regulation and neurotrophic activity, a relationship which has, to date, not been well studied. These results are also notable given that iron dysregulation occurs in most neurodegenerative disease settings, and that iron has been shown to facilitate protein aggregation and apoptotic mechanisms.