Gene

PDE10A

Neuroscience

Phosphodiesterase

Guanosine monophosphate

Cyclic guanosine monophosphate

Clinical trial

Receptor

Nitric oxide

Alzheimer's disease

Biochemistry

Second messenger system

Organic chemistry

Psychology

Nucleotide

Enzyme

Internal medicine

Pharmacology

Guanosine

Cyclic adenosine monophosphate

Medicine

Chemistry

Disease

Journal of Medicinal Chemistry

Alzheimer's disease (AD) is one of the greatest public health challenges. Phosphodiesterases (PDEs) are a superenzyme family responsible for the hydrolysis of two second messengers: cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Since several PDE subfamilies are highly expressed in the human brain, the inhibition of PDEs is involved in neurodegenerative processes by regulating the concentration of cAMP and/or cGMP. Currently, PDEs are considered as promising targets for the treatment of AD since many PDE inhibitors have exhibited remarkable cognitive improvement effects in preclinical studies and over 15 of them have been subjected to clinical trials. The aim of this review is to summarize the outstanding progress that has been made by PDE inhibitors as anti-AD agents with encouraging results in preclinical studies and clinical trials. The binding affinity, pharmacokinetics, underlying mechanisms, and limitations of these PDE inhibitors in the treatment of AD are also reviewed and discussed.

Novel Phosphodiesterase Inhibitors for Cognitive Improvement in Alzheimer’s Disease