Title:Cyclic Nucleotides Signaling and Phosphodiesterase Inhibition: Defying Alzheimer’s Disease
Volume: 21
Issue: 13
关键词:
阿尔茨海默病，认知，cAMP
摘要: Defects in brain functions associated with aging and neurodegenerative diseases benefit insignificantly
from existing options, suggesting that there is a lack of understanding of pathological
mechanisms. Alzheimer’s disease (AD) is such a nearly untreatable, allied to age neurological deterioration
for which only the symptomatic cure is available and the agents able to mould progression of
the disease, is still far away. The altered expression of phosphodiesterases (PDE) and deregulated cyclic
nucleotide signaling in AD has provoked a new thought of targeting cyclic nucleotide signaling in
AD. Targeting cyclic nucleotides as an intracellular messenger seems to be a viable approach for certain
biological processes in the brain and controlling substantial. Whereas, the synthesis, execution,
and/or degradation of cyclic nucleotides has been closely linked to cognitive deficits. In relation to
cognition, the cyclic nucleotides (cAMP and cGMP) have an imperative execution in different phases
of memory, including gene transcription, neurogenesis, neuronal circuitry, synaptic plasticity and neuronal
survival, etc. AD is witnessed by impairments of these basic processes underlying cognition,
suggesting a crucial role of cAMP/cGMP signaling in AD populations. Phosphodiesterase inhibitors
are the exclusive set of enzymes to facilitate hydrolysis and degradation of cAMP and cGMP thereby,
maintains their optimum levels initiating it as an interesting target to explore. The present work reviews
a neuroprotective and substantial influence of PDE inhibition on physiological status, pathological
progression and neurobiological markers of AD in consonance with the intensities of cAMP and
cGMP.
