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Targeting the SUMO pathway for neuroprotection in brain ischaemia
  1. Wei Yang1,
  2. Huaxin Sheng1,
  3. Haichen Wang2
  1. 1Multidisciplinary Neuroprotection Laboratories, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA
  2. 2Multidisciplinary Neuroprotection Laboratories, Department of Neurology, Duke University Medical Center, Durham, North Carolina, USA
  1. Correspondence to Dr Wei Yang; wei.yang{at}duke.edu

Abstract

Small ubiquitin-like modifier (SUMO) conjugation (SUMOylation) is a post-translational protein modification that modulates almost all major cellular processes, and has been implicated in many human diseases. A growing body of evidence from in vitro and in vivo studies demonstrates that increasing global levels of SUMO conjugated proteins (global SUMOylation) protects cells against ischaemia-induced damage, while suppressing global SUMOylation promotes cell injury after ischaemia. Indeed, SUMOylation has emerged as a potential therapeutic target for neuroprotection in brain ischaemia, including global brain ischaemia and focal brain ischaemia (ischaemic stroke). Here, we summarise findings on the role of SUMOylation in human diseases, brain ischaemia in particular, and review recent developments in drug discovery targeting SUMOylation with a major focus on its neuroprotective applications.

  • SUMO
  • brain ischemia
  • neuroprotection
  • drug discovery
  • SENP inhibitors

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Footnotes

  • Contributors WY conceived and drafted the review with critical input from HS and HW.

  • Funding This study was partly supported by American Heart Association grant number 12SDG11950003 and National Institutes of Health (NIH) grant number NS081299.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.