Abstract:

Phosphodiesterase 10A (PDE10A) is the only member of the tenth family of phosphodiesterases and hydrolyzes the ubiquitous second messengers, i.e. cyclic adenosine 3′,5′-monophosphate (cAMP) and cyclic guanosine 3′,5′-monophosphate (cGMP), thus involves in the regulation of a number of intracellular signal transduction pathways. High expression in striatum of brain suggests that PDE10A involves in the development of diseases related to striatal dysfunction. In addition, the PDE10A level of patients with some peripheral diseases significantly increased in the tissue cells. So PDE10A is likely to play an important role in the genesis and development of many diseases. Despite medicine researches and drug development pay more and more attention on PDE10A, a lot of problems still exist in terms of studies on its structure, functions, and regulatory mechanisms of physiology and pathology. Especially the failure of a specific inhibitor of PDE10A, PF-2545920 (MP-10), for the treatment of schizophrenia in phaseⅡ clinical trials drives people to reexamine the roles of PDE10A in central nervous system and whether PDE10A is a suitable therapeutic target. So this paper summarizes the basic characteristics, structure, and functions of PDE10A and related diseases and hopes to be helpful for further study and application.

Key words: phosphodiesterase, phosphodiesterase 10A (PDE10A), phosphodiesterase inhibitors, striatum, schizophrenia, Huntington's disease