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FASEB J. 2018 Mar;32(3):1677-1691. doi: 10.1096/fj.201700711R. Epub 2018 Jan 3.

Quantitative high-throughput screening identifies cytoprotective molecules that enhance SUMO conjugation via the inhibition of SUMO-specific protease (SENP)2.

Author information

1
Stroke Branch, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland, USA.
2
Division of Stem Cell Neurobiology, Department of Clinical Neurosciences, Wellcome Trust-Medical Research Council Stem Cell Institute and National Institute of Health Research Biomedical Research Centre, University of Cambridge, United Kingdom.
3
UAB School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
4
National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA; and.
5
Center for Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA.

Abstract

The development of novel neuroprotective treatments for acute stroke has been fraught with failures, which supports the view of ischemic brain damage as a highly complex multifactorial process. Post-translational modifications such as small ubiquitin-like modifier (SUMO)ylation have emerged as critical molecular regulatory mechanisms in states of both homeostasis and ischemic stress, as evidenced by our previous work. Accordingly, the clinical significance of the selective control of the global SUMOylation process has become apparent in studies of ischemic pathobiology and pathophysiology. Herein, we describe a process capable of identifying and characterizing small molecules with the potential of targeting the SUMO system through inhibition of SUMO deconjugation in an effort to develop novel stroke therapies.-Bernstock, J. D., Ye, D., Smith, J. A., Lee, Y.-J., Gessler, F. A., Yasgar, A., Kouznetsova, J., Jadhav, A., Wang, Z., Pluchino, S., Zheng, W., Simeonov, A., Hallenbeck, J. M., Yang, W. Quantitative high-throughput screening identifies cytoprotective molecules that enhance SUMO-conjugation via the inhibition of SUMO-specific protease (SENP)2.

KEYWORDS:

SUMOylation; drug repurposing; ischemia; neuroprotection; stroke

PMID:
29146736
PMCID:
PMC5892725
DOI:
10.1096/fj.201700711R
[Indexed for MEDLINE]
Free PMC Article

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