Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors

Several β-secretase (BACE) inhibitors exhibit unexplained ocular toxicity in preclinical studies. Here the authors generate a clickable photoaffinity probe to interrogate off-targets in cells and animals, and identify inhibition of cathepsin D as a driver of ocular toxicity.

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Autores principales:	Andrea M. Zuhl, Charles E. Nolan, Michael A. Brodney, Sherry Niessen, Kevin Atchison, Christopher Houle, David A. Karanian, Claude Ambroise, Jeffrey W. Brulet, Elizabeth M. Beck, Shawn D. Doran, Brian T. O’Neill, Christopher W. am Ende, Cheng Chang, Kieran F. Geoghegan, Graham M. West, Joshua C. Judkins, Xinjun Hou, David R. Riddell, Douglas S. Johnson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2016
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/5dfe4a29e6af43a49ee6c24207abc513
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spelling	oai:doaj.org-article:5dfe4a29e6af43a49ee6c24207abc5132021-12-02T17:32:50ZChemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors10.1038/ncomms130422041-1723https://doaj.org/article/5dfe4a29e6af43a49ee6c24207abc5132016-10-01T00:00:00Zhttps://doi.org/10.1038/ncomms13042https://doaj.org/toc/2041-1723Several β-secretase (BACE) inhibitors exhibit unexplained ocular toxicity in preclinical studies. Here the authors generate a clickable photoaffinity probe to interrogate off-targets in cells and animals, and identify inhibition of cathepsin D as a driver of ocular toxicity.Andrea M. ZuhlCharles E. NolanMichael A. BrodneySherry NiessenKevin AtchisonChristopher HouleDavid A. KaranianClaude AmbroiseJeffrey W. BruletElizabeth M. BeckShawn D. DoranBrian T. O’NeillChristopher W. am EndeCheng ChangKieran F. GeogheganGraham M. WestJoshua C. JudkinsXinjun HouDavid R. RiddellDouglas S. JohnsonNature PortfolioarticleScienceQENNature Communications, Vol 7, Iss 1, Pp 1-14 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Andrea M. Zuhl Charles E. Nolan Michael A. Brodney Sherry Niessen Kevin Atchison Christopher Houle David A. Karanian Claude Ambroise Jeffrey W. Brulet Elizabeth M. Beck Shawn D. Doran Brian T. O’Neill Christopher W. am Ende Cheng Chang Kieran F. Geoghegan Graham M. West Joshua C. Judkins Xinjun Hou David R. Riddell Douglas S. Johnson Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors
description	Several β-secretase (BACE) inhibitors exhibit unexplained ocular toxicity in preclinical studies. Here the authors generate a clickable photoaffinity probe to interrogate off-targets in cells and animals, and identify inhibition of cathepsin D as a driver of ocular toxicity.
format	article
author	Andrea M. Zuhl Charles E. Nolan Michael A. Brodney Sherry Niessen Kevin Atchison Christopher Houle David A. Karanian Claude Ambroise Jeffrey W. Brulet Elizabeth M. Beck Shawn D. Doran Brian T. O’Neill Christopher W. am Ende Cheng Chang Kieran F. Geoghegan Graham M. West Joshua C. Judkins Xinjun Hou David R. Riddell Douglas S. Johnson
author_facet	Andrea M. Zuhl Charles E. Nolan Michael A. Brodney Sherry Niessen Kevin Atchison Christopher Houle David A. Karanian Claude Ambroise Jeffrey W. Brulet Elizabeth M. Beck Shawn D. Doran Brian T. O’Neill Christopher W. am Ende Cheng Chang Kieran F. Geoghegan Graham M. West Joshua C. Judkins Xinjun Hou David R. Riddell Douglas S. Johnson
author_sort	Andrea M. Zuhl
title	Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors
title_short	Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors
title_full	Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors
title_fullStr	Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors
title_full_unstemmed	Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors
title_sort	chemoproteomic profiling reveals that cathepsin d off-target activity drives ocular toxicity of β-secretase inhibitors
publisher	Nature Portfolio
publishDate	2016
url	https://doaj.org/article/5dfe4a29e6af43a49ee6c24207abc513
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Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors

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