Phosphodiesterase Inhibitors: A Therapeutic Augmentation for Treatment of Cognitive Impairment

Abstract

Cognitive dysfunction is a loss of intellectual skills. This can affect the thoughts, memories and abilities of reasoning of a person. Dementia is considered to be one of the cognitive dysfunction neuropsychological hallmarks. It is estimated to be prevalent in around 81.1 million people worldwide by 2040. Significant progress has been made in understanding the pathological basis of these disorders over the last few decades. In experimental models of neurological disease, the transmutation of intracellular signalling pathways involving cognitive deficits, synaptic dysfunction, loading of β-amyloid plaques or presynaptic density in hippocampus has demonstrated a therapeutic benefit. Cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP) are two such targets for intracellular signalling, which produced beneficial cellular effects in CNS pathologies after elevation. These second messengers strengthen signals at cell surface receptors and within the cell, making them an essential element in signal transduction and necessary for cellular signalling in various cell functions such as the release of neurotransmitters. Although the concentration of cyclic nucleotides depends on the rate of their synthesis by adenylate or guanylate cyclase’s, however, their breakdown is regulated through phosphodiesterase’s (PDEs) which are capable of employ tight, selective control over cyclic nucleotide signaling through the hydrolysis of cAMP/cGMP. PDE inhibition is therefore thought to be a new strategy for building cyclic nucleotide levels in the brain. This review evaluated recent studies and development with a focus on cognitive decline, but due to adverse effects, there are still very few PDE inhibitors for clinical use in neurology. Therefore, more specific inhibitors must be looked for at the level of PDE subclasses and their isoforms.