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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2016
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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. |
format | Online Article Text |
id | pubmed-4927884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
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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