Opportunities and perspectives of small molecular phosphodiesterase inhibitors in neurodegenerative diseases

Eur J Med Chem. 2024 Apr 6;271:116386. doi: 10.1016/j.ejmech.2024.116386. Online ahead of print.ABSTRACTPhosphodiesterase (PDE) is a superfamily of enzymes that are responsible for the hydrolysis of two second messengers: cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). PDE inhibition promotes the gene transcription by activating cAMP-response element binding protein (CREB), initiating gene transcription of brain-derived neurotrophic factor (BDNF). The procedure exerts neuroprotective profile, and motor and cognitive improving efficacy. From this point of view, PDE inhibition will provide a promising therapeutic strategy for treating neurodegenerative disorders. Herein, we summarized the PDE inhibitors that have entered the clinical trials or been discovered in recent five years. Well-designed clinical or preclinical investigations have confirmed the effectiveness of PDE inhibitors, such as decreasing Aβ oligomerization and tau phosphorylation, alleviating neuro-inflammation and oxidative stress, modulating neuronal plasticity and improving long-term cognitive impairment.PMID:38614063 | DOI:10.1016/j.ejmech.2024.116386
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Source Type: research