Related Experiment Video
Updated: Nov 21, 2025

Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes
Published on: July 23, 2016
A Perspective on Natural and Nature-Inspired Small Molecules Targeting Phosphodiesterase 9 (PDE9): Chances and
Giovanni Ribaudo1, Maurizio Memo1, Alessandra Gianoncelli1
1Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy.
Abstract:
As life expectancy increases, dementia affects a growing number of people worldwide. Besides current treatments, phosphodiesterase 9 (PDE9) represents an alternative target for developing innovative small molecules to contrast neurodegeneration. PDE inhibition promotes neurotransmitter release, amelioration of microvascular dysfunction, and neuronal plasticity. This review will provide an update on natural and nature-inspired PDE9 inhibitors, with a focus on the structural features of PDE9 that encourage the development of isoform-selective ligands. The expression in the brain, the presence within its structure of a peculiar accessory pocket, the asymmetry between the two subunits composing the protein dimer, and the selectivity towards chiral species make PDE9 a suitable target to develop specific inhibitors. Additionally, the world of natural compounds is an ideal source for identifying novel, possibly asymmetric, scaffolds, and xanthines, flavonoids, neolignans, and their derivatives are currently being studied. In this review, the available literature data were interpreted and clarified, from a structural point of view, taking advantage of molecular modeling: 3D structures of ligand-target complexes were retrieved, or built, and discussed.
More Related Videos
11:44Cellular Membrane Affinity Chromatography Columns to Identify Specialized Plant Metabolites Interacting with Immobilized Tropomyosin Kinase Receptor B
Published on: January 19, 2022
09:44Chemogenetic Regulation in Reprogrammed Stem Cell-derived Precursor Cells in Treating Neurodegenerative Diseases
Published on: May 2, 2025
Related Concept Videos
Drugs Affecting Neurotransmitter Synthesis
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
siRNA - Small Interfering RNAs
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
Protein Kinases and Phosphatases
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Alzheimer's Disease: Treatment