cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A) (PDE10A)

cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A) is a dual-substrate enzyme that regulates intracellular signaling by hydrolyzing the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) [1.1.1, 1.2.1]. It is uniquely and highly expressed in the medium spiny neurons of the striatum, a brain region critical for motor control, emotion, and cognition [1.2.1, 1.2.5]. By modulating the levels of these cyclic nucleotides, PDE10A influences downstream signaling pathways, including the protein kinase A (PKA) and cAMP-response element-binding protein (CREB) cascades [1.2.4, 1.4.1]. Dysregulation of PDE10A has been linked to several neuropsychiatric and neurodegenerative disorders, most notably schizophrenia, Huntington's disease, and Parkinson's disease [1.2.1, 1.2.2]. Pharmacological inhibition of PDE10A is a therapeutic strategy aimed at enhancing striatal signaling to alleviate symptoms of these conditions without the side effects associated with direct dopamine receptor blockade [1.1.1, 1.4.4]. While several selective PDE10A inhibitors have reached clinical trials, achieving consistent efficacy in schizophrenia remains a significant challenge [1.2.2, 1.4.4]. Additionally, PDE10A has emerged as a potential biomarker and target in certain cancers and metabolic disorders [1.1.2, 1.4.1]. The enzyme's localized expression makes it an attractive target for precision medicine in central nervous system disorders [1.2.5, 1.4.4].

Other names

PDE10HSPDE10AHSPDE10A19ADSD2IOLODPhosphodiesterase 10AcAMP/cGMP-specific phosphodiesterase 10A

Inhibition of the PDE10A enzyme, which prevents the breakdown of cAMP and cGMP, leading to elevated levels of these cyclic nucleotides in neurons and enhanced downstream signaling, particularly in the striatum [1.1.1, 1.2.1].