title: PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease.
abstract: Phosphodiesterase 5 (PDE5) is a critical component of the cGMP-PKG axis of cellular signaling in neurons, and inhibition of PDE5 has been shown to be therapeutic in a wide range of neurologic conditions in animal models. However, enthusiasm for PDE5 inhibitors in humans is limited by data suggesting that PDE5 may not exist in human neurons. Here, we first show that past attempts to quantify PDE5 mRNA were flawed due to the use of incorrect primers, and that when correct primers are used, PDE5 mRNA is detectable in human brain tissue. We then show that PDE5 protein exists in human brain by western blot and ELISA. Most importantly, we performed immunohistochemistry and demonstrate that PDE5 is present in human neurons. We hope that this work will trigger a renewed interest in the development of PDE5 inhibitors for neurologic disease.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.|Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Teich
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.|Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
authors.forename: Mikako
authors.initials: M
authors.lastname: Sakurai
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.|Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
authors.forename: Mitesh
authors.initials: M
authors.lastname: Patel
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.|Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
authors.forename: Cameron
authors.initials: C
authors.lastname: Holman
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.|Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
authors.forename: Faisal
authors.initials: F
authors.lastname: Saeed
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.|Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
authors.forename: Jole
authors.initials: J
authors.lastname: Fiorito
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.|Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
authors.forename: Ottavio
authors.initials: O
authors.lastname: Arancio
mesh_terms: D015153:Blotting, Western; D001921:Brain / Q000201:enzymology*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D009422:Nervous System Diseases / Q000188:drug therapy; D009474:Neurons / Q000201:enzymology*; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D017931:DNA Primers; D058986:Phosphodiesterase 5 Inhibitors; D012333:RNA, Messenger; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5
keywords: Alzheimer’s disease; PDE5 inhibitors; memory; phosphodiesterase 5