Translational Stroke Research

, Volume 9, Issue 2, pp 157–173 | Cite as

Protein Modifications with Ubiquitin as Response to Cerebral Ischemia-Reperfusion Injury

Original Article


Post-translational protein modifications present an elegant and energy efficient way to dynamically reprogram cellular protein properties and functions in response to homeostatic imbalance. One such protein modification is the tagging of proteins with the small modifier ubiquitin that can have an impact on protein stability, localization, interaction dynamics, and function. Ubiquitination is vital to any eukaryotic cell under physiological conditions, but even more important under stress including oxidative, genotoxic, and heat stress, where ubiquitination levels are drastically increased. Elevated levels of ubiquitin-protein conjugates are also observed in the brain after focal and global cerebral ischemia. Post-ischemic ubiquitination is immediately induced with reperfusion and transiently detected in neurons with survival potential located in the peri-infarct area. This review aims to critically discuss current knowledge and controversies on protein ubiquitination after cerebral ischemia, with special emphasis on potential mechanisms leading to elevated ubiquitination and on target identification. Further, possible functional implications of post-ischemic ubiquitination, including a relationship to SUMOylation, a neuroprotective modification, will be highlighted. The elevation in ubiquitinated proteins following cerebral ischemia is a greatly under-explored research area, the better understanding of which may contribute to the development of novel stroke therapies.


Cerebral ischemia Reperfusion Ubiquitin Proteasome SUMO Neuronal stress response 


Compliance with Ethical Standards

Conflict of Interest

The author declares that she has no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by the author.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Feil Family Brain and Mind Research InstituteWeill Cornell MedicineNew YorkUSA

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