In line with this, the characterization of the effects of a pharmacological inhibition of PDE indirectly suggests that the reduction of PDE activity in HD could lead to multiple effects: it up-regulates cAMP-responsive element –dependent transcription, it down-regulates HDAC4 (histone deacetylase 4) mRNA, and could activate Mitogen- and stress-activated kinase-1 (MSK1). The gene discussed is RPS6KA5; the disease is Huntington disease.