Phosphodiseterases (PDEs), a superfamily of 11 en zymes (PDE1-11) that hydrolyze cyclic nucleotides (cAMP and cGMP), mediate a variety of peripheral and central functions.PDE inhibitors can be used for treatment of various diseases, in cluding peripheral diseases such as chronic obstructive pulmona ry disease (COPD), sexual dysfunction, and heart failures, and CNS disorders such as Alzheimers disease, depression, schizo phrenia, anxiety, alcoholism, Parkinsons disease, Huntingtons disease, and stroke.While to date there have been no PDE in hibitors approved for clinic utility for CNS disorders, significant progresses have been made in preclinical and clinical studies in this area.More specifically, we have found that inhibition of PDE4, which specifically catalyzes the hydrolysis of cAMP, re versed memory deficits produced by hippocampal infusions of βamyloid peptide 1-42 (Aβ1-42).Consistent with this, the PDE4 inhibitor rolipram also attenuated Aββ42-induced inflamma tory responses, apoptosis, and deficit in cAMP/CREB signaling in the hippocampus.0n addition, using mice deficient in a spe cific PDE4 subtype (PDF4A, 4B, or 4D), we identified that PDE4A and PDE4D may be the major subtypes in these proces ses.