cAMP-specific 3',5'-cyclic phosphodiesterase 10A (PDE10A)

cAMP-specific 3',5'-cyclic phosphodiesterase 10A (PDE10A) is a dual-substrate enzyme that hydrolyzes both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), with a significantly higher affinity for cAMP (UniProt: Q9Y233). It is uniquely characterized by its highly localized expression within the medium spiny neurons of the striatum, positioning it as a master regulator of basal ganglia circuitry (PubMed: 21835188). By modulating the levels of these second messengers, PDE10A influences both the direct and indirect striatal pathways, which are essential for motor coordination and executive function (NCBI Gene: 10846). In the context of schizophrenia, PDE10A inhibitors are investigated for their ability to enhance dopaminergic signaling and improve cognitive symptoms (PubMed: 25159930). Furthermore, PDE10A levels are known to decline early in Huntington's disease, making the enzyme a valuable biomarker for disease progression and a target for potential neuroprotective therapies (PubMed: 24991464). While several selective inhibitors like PF-02545920 and TAK-063 have been evaluated in clinical trials, achieving the desired efficacy profile remains a significant challenge in drug development (PubChem: CID 10198500).

Other names

Phosphodiesterase 10APDE10HSPDE10AFLJ11894PDE10A1PDE10A2

Selective inhibition of the PDE10A enzyme to prevent the hydrolysis of cAMP and cGMP, thereby increasing their intracellular concentrations and modulating neuronal signaling in the striatum (PubMed: 21835188).