| Abstrak/Abstract |
Phosphodiesterase-1 (PDE1) is a versatile enzyme that has surprisingly received considerable 48 attention as a possible therapeutic target in Alzheimer’s disease (AD) because it maintains the 49 homeostasis of 3ʹ,5ʹ-cyclic adenosine monophosphate (cAMP) and 3ʹ,5ʹ-cyclic guanosine 50 monophosphate (cGMP) in the brain. cAMP and cGMP are the two key second messengers that 51 regulate a broad range of intracellular processes and neurocognitive functions, specifically 52 memory and cognition, associated with AD. However, the lack of available selective drugs on 53 the market poses challenges to identifying the beneficial effects of natural products. The present 54 review focuses on PDE1 and its isoforms, splicing variants, location, distribution, and function; 55 the role of PDE1 inhibitors in AD; and the use of vinpocetine and natural products as specific 56 PDE1 inhibitors. Moreover, it aims to provide ongoing updates, identify research gaps, and
57 present future perspectives. This review indicates the potential role of PDE1 inhibitors in the 58 treatment of neurodegenerative disorders, such as AD. Certain clinical trials on the alleviation of 59 AD in patients are still in progress. Among de novo outcomes, the employment of PDE1 60 inhibitors to treat AD is an important advancement given the absence of particular therapies in 61 the pipeline for this highly prevalent disease. To sum up, PDE1 inhibition has been specifically 62 proposed as a critical therapeutic approach for AD. This study provides a comprehensive review 63 on the biological and pharmacological aspects of PDE1, its role on the Alzheimer’s diseases and 64 its significance as AD therapeutic target in drug discovery from natural products. This review 65 will help clinical trials and scientific research exploring new entities for the treatment and 66 prevention of AD |
