Title:Phosphodiesterase: An Interface Connecting Cognitive Deficits to Neuropsychiatric and Neurodegenerative Diseases
Volume: 21
Issue: 3
Author(s): Zhen-Zhen Wang, Yi Zhang, Han-Ting Zhang and Yun-Feng Li
Affiliation:
Keywords:
Phosphodiesterase, cognitive deficit, neuropsychiatric disease, neurodegenerative diseases, cyclic AMP, cyclic GMP, PDE4 subtype,
splice variant.
Abstract: 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.
