This stable proNGF molecule demonstrated proapoptotic activity on rat pheocytochroma PC12 cells, PC12nnr cells, C6 glioblastoma cells, and RN22 schwannoma cells.
The neurotrophin family includes structurally related proteins that promote the survival, growth, and maintenance of neurons in the central and peripheral nervous systems ( 1). Nerve growth factor (NGF), the first member of the family, was discovered by Levi-Montalcini and coworkers ( 2) over 50 years ago. Other members of the family include brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5, and NT-6 ( 1– 4). Neurotrophins play a crucial role in neuronal survival, differentiation, growth, and apoptosis ( 5). Each neurotrophin binds to a 140-kDa tyrosine kinase receptor, Trk receptor.
NGF binds to TrkA, BDNF and NT-4/5 selectively bind to TrkB, and NT-3 binds to TrkC ( 1, 6). In addition to a selective Trk receptor for each neurotrophin, there is a common neurotrophin receptor (NTR), p75 NTR ( 7, 8). The two receptors, Trk and p75 NTR, are structurally unrelated with neurotrophins interacting primarily with the Ig-like C2 (IgGC2) domain of the Trk receptors but with the cysteine-rich domains of the p75 NTR receptor ( 9– 11). Neurotrophin binding to the Trk receptors transduces positive signals like growth, survival, or differentiation, whereas binding to the p75 NTR/Trk heterodimer can transduce positive or negative signals ( 12– 16).
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