Increased expression of cyclin
D1 has also been reported in trophic factor-deprived sympathetic neurons,
160,161 raising the possibility that inappropriate entry into S phase might
play a role in triggering neuronal PCD. Studies showing that the synthesized
cyclin D1 pairs with a cyclin-dependent kinase and actually alters cell cycle
distribution remain to be performed. Nonetheless, experiments demonstrating
that the cyclin D1-dependent kinase inhibitor p16INK4 and low-molecular
weight inhibitors of cell cycle progression such as mimosine, olomucine, and
flavopiridol can inhibit PCD in NGF-deprived sympathetic neurons or neuronally
differentiated PC12 pheochromocytoma cells162,163 provide further
support for a model in which inappropriate cell cycle progression after
neutrophin withdrawal contributes to PCD.