Phosphodiesterase: An Interface Connecting Cognitive Deficits to Neuropsychiatric and Neurodegenerative Diseases

Phosphodiesterases (PDEs) are the only known enzymes to degrade intracellular cyclic AMP and/or cyclic GMP. The PDE superfamily consists of 11 families (PDE1– PDE11), each of which has 1 to 4 subtypes. Some of the subtypes may have multiple splice variants (e.g. PDE4D1–PDE4D11), leading to a total of more than 100 known proteins to date. Growing attention has been paid to the potential of PDEs as therapeutic targets for mood disorders and/or diseases affecting cognitive activity by controlling the rate of hydrolysis of the two aforementioned second messengers in recent years. The loss of cognitive functions is one of the major complaints most patients with CNS diseases face; it has an even more prominent negative impact on the quality of daily life. Cognitive dysfunction is usually a prognosis in patients suffering from neuropsychiatric and neurodegenerative diseases, including depression, schizophrenia, and Alzheimer’s disease. This review will focus on the contributions of PDEs to the interface between cognitive deficits and neuropsychiatric and neurodegenerative disorders. It is expected to make for the understanding and discovery that selective PDE inhibitors have the therapeutic potential for cognitive dysfunctions associated with neuropsychiatric and neurodegenerative disorders.