cAMP/PKA-CREB-BDNF Signaling Cascade and Phosphodiesterase 4 Inhibition: A Possible Neuroprotective Approach in Alzheimer’s Disease | ||
| Records of Pharmaceutical and Biomedical Sciences | ||
| Volume 8, Issue 1, 2024, Pages 158-168 PDF (802.67 K) | ||
| Document Type: Mini-reviews | ||
| DOI: 10.21608/rpbs.2024.301889.1309 | ||
| Author | ||
| Soha Mohamed Atya* | ||
| Biochemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt | ||
| Abstract | ||
| Alzheimer’s disease (AD) is the most common cause of age-related dementia worldwide. It is a neurodegenerative disease characterized by cerebral plaques containing amyloid-β (Aβ) peptide aggregates, intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated tau proteins, and neuroinflammation with subsequent death of neurons and brain tissue damage. There is currently no treatment available for the disease or even to halt its progress. Therefore, targeting the etiologic pathologies finding new agents is a crucial requirement. It is speculated that Aβ-induced downregulation of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) protein, a biological component essential for learning and memory, causes cognitive impairments in AD. Phosphodiesterase (PDE4) inhibitors have been shown to improve AD manifestations by restoring synaptic function through the activation of the cAMP/PKA-CREB-BDNF signaling cascade. Cilomilast (CILO) is a potent selective inhibitor of PDE4 with anti-inflammatory effect that is currently tested in phase III clinical trials as a possible treatment for chronic obstructive pulmonary disease (COPD). Chlorogenic acid (CGA), is a major polyphenol in Coffea that possesses neuroprotective, anti-inflammatory, and anti-oxidative properties. Augmented PDE4 inhibition may be demonstrated through the co-administration of CGA and CILO, which implies that PDE4 inhibitors may serve as potential neuroprotective molecules. | ||
| Keywords | ||
| Alzheimer’s; phosphodiesterase 4, CREB. | ||
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