Therapeutic Potential of Phosphodiesterase Inhibitors against Neurodegeneration: The Perspective of the Medicinal Chemist

data. In the context of drug repurposing, a section focusing on PDE5 was introduced. Original computational studies were performed to rationalize the emerging evidence that suggests the role of PDE5 inhibitors as multi-target agents against neurodegeneration. Moreover, since such compounds must cross the blood-brain barrier and reach inhibitory concentrations in the central nervous system to exert their therapeutic activity, physicochemical parameters were analyzed and discussed. Taken together, literature and computational data suggest that some PDE5 inhibitors, such as tadalafil, represent promising candidates.