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PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease

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...

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Autores principales: Teich, Andrew F., Sakurai, Mikako, Patel, Mitesh, Holman, Cameron, Saeed, Faisal, Fiorito, Jole, Arancio, Ottavio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927884/
https://www.ncbi.nlm.nih.gov/pubmed/26967220
http://dx.doi.org/10.3233/JAD-151104
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author Teich, Andrew F.
Sakurai, Mikako
Patel, Mitesh
Holman, Cameron
Saeed, Faisal
Fiorito, Jole
Arancio, Ottavio
author_facet Teich, Andrew F.
Sakurai, Mikako
Patel, Mitesh
Holman, Cameron
Saeed, Faisal
Fiorito, Jole
Arancio, Ottavio
author_sort Teich, Andrew F.
collection PubMed
description 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.
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spelling pubmed-49278842016-06-30 PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease Teich, Andrew F. Sakurai, Mikako Patel, Mitesh Holman, Cameron Saeed, Faisal Fiorito, Jole Arancio, Ottavio J Alzheimers Dis Research Article 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. IOS Press 2016-04-26 /pmc/articles/PMC4927884/ /pubmed/26967220 http://dx.doi.org/10.3233/JAD-151104 Text en IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Teich, Andrew F.
Sakurai, Mikako
Patel, Mitesh
Holman, Cameron
Saeed, Faisal
Fiorito, Jole
Arancio, Ottavio
PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease
title PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease
title_full PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease
title_fullStr PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease
title_full_unstemmed PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease
title_short PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease
title_sort pde5 exists in human neurons and is a viable therapeutic target for neurologic disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927884/
https://www.ncbi.nlm.nih.gov/pubmed/26967220
http://dx.doi.org/10.3233/JAD-151104
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