Rolipram

Rolipram has been observed to selectively inhibit cAMP-phosphodiesterase (PDE4) by recruiting PDE4 into cytosolic aggregates that are not membrane-encapsulated. A down-stream effect of this observation is the inhibition of autophagy. Under normal conditions, autophagosomes are coated with the autophagic marker light chain 3 (LC3). LC3 binds directly to p62 protein, which shuttles protein to aggresomes, eventually leading to an autophagic event. In the absence of LC3, protein aggregates will not undergo autophagy, and will remain as cytosolic aggregates, as seen with the inhibition of PDE4 by Rolipram. It promotes axonal regeneration (4).

1. Kato H., et al. (1995) Eur J Pharmacol. 272(1): 107-10. 2. Christian F., et al. (2010) Cell Signal. 22(10): 1576-96. 3. Houslay M.D., & Christian F. (2010) Autophagy. 6(8): 1198-200. 4. E Nikulina et al PNAS; 2004; 101, 8786