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.
Main Authors: | 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 |
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Format: | Article |
Language: | English |
Published: |
Nature Publishing Group
2016-10-01
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Series: | Nature Communications |
Online Access: | https://doi.org/10.1038/ncomms13042 |
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