Title:Diabetic Theory in Anti-Alzheimer’s Drug Research and Development. Part 2: Therapeutic Potential of cAMP-Specific Phosphodiesterase Inhibitors
Volume: 28
Issue: 18
Author(s): Agnieszka Jankowska, Maciej Pawłowski and Grażyna Chłoń-Rzepa*
Affiliation:
- Jagiellonian University Medical College, Faculty of Pharmacy, Department of Medicinal Chemistry, 9 Medyczna Street, Krakow 30-688,Poland
Keywords:
Alzheimer's disease, PDE inhibitor, anti-inflammatory activity, antidiabetic activity, cAMP, cognitive
impairment, neuroinflammation, phosphodiesterase.
Abstract: Alzheimer’s disease (AD) is one of the most prevalent age-related neurodegenerative
disease that affects the cognition, behavior, and daily activities of individuals. Studies indicate
that this disease is characterized by several pathological mechanisms, including the accumulation
of amyloid-beta peptide, hyperphosphorylation of tau protein, impairment of cholinergic
neurotransmission, and increase in inflammatory responses within the central nervous
system. Chronic neuroinflammation associated with AD is closely related to disturbances in
metabolic processes, including insulin release and glucose metabolism. As AD is also called
type III diabetes, diverse compounds having antidiabetic effects have been investigated as potential
drugs for its symptomatic and disease-modifying treatment. In addition to insulin and
oral antidiabetic drugs, scientific attention has been paid to cyclic-3′,5′-adenosine monophosphate
(cAMP)-specific phosphodiesterase (PDE) inhibitors that can modulate the concentration
of glucose and related hormones and exert beneficial effects on memory, mood, and emotional
processing. In this review, we present the most recent reports focusing on the involvement
of cAMP-specific PDE4, PDE7, and PDE8 in glycemic and inflammatory response controls
as well as the potential utility of the PDE inhibitors in the treatment of AD. Besides the
results of in vitro and in vivo studies, the review also presents recent reports from clinical trials.
