High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (PDE8B)

High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (PDE8B) is a cyclic nucleotide phosphodiesterase enzyme highly specific for the hydrolysis of cyclic AMP (cAMP), a crucial signaling molecule in numerous physiological processes[1][6][7]. It does not hydrolyze cGMP and is resistant to inhibition by the classical PDE inhibitor IBMX[1][3]. PDE8B regulates intracellular cAMP levels in endocrine tissues—especially the thyroid and adrenal glands—as well as in the brain, particularly in the hippocampus and striatum, influencing hormone production, steroidogenesis, cell proliferation, and cognitive and motor functions[3]. Mutations in PDE8B cause autosomal dominant striatal degeneration (ADSD) and are implicated in pigmented nodular adrenocortical disease (Cushing’s syndrome)[1][3]. Increased expression or variants are associated with altered thyroid hormone profiles and may serve as genetic or transcriptomic biomarkers for diseases such as Alzheimer’s and thyroid dysfunction[3]. Though therapeutic interest in PDE8B antagonists exists for cognitive enhancement and endocrine disorders, safety concerns around anxiety and affective changes remain a challenge for drug development[2][5].

Other names

phosphodiesterase 8BPDE8Bcell proliferation-inducing gene 22 proteinPIG22HsPDE8BADSDPPNAD33',5'-cyclic nucleotide phosphodiesterase 8B

Inhibition of PDE8B increases cellular cAMP, potentially enhancing cognitive/motor function and steroidogenesis, but may induce anxiety or alter affect[2][5]