Hypoxia-ischaemia and reperfusion (HI/R) damage is a result stemming from any event that interrupts the brain's blood supply, such as the occlusion of a blood vessel. In neurons, the molecular mechanisms involved in the HI/R cascade are diverse in nature, ranging from proteomic, genomic, and transcriptomic alterations in the cells. Many of these changes are governed by post-translational modifications such as SUMOylation, which can quickly and reversibly alter the fate of key proteins. This review summarises current evidence regarding the role of SUMOylation in key molecular pathways in major in vivo and in vitro models of cerebral HI/R. Our review reinforces the concept of SUMOylation being a dynamic and time-dependent process that functions as a rapid molecular switch, affecting major pathways across different cell types and cellular compartments. Moreover, the context-dependent pathological and neuroprotective action of SUMOylation in different pathways involved in HI/R is explored. It sheds light on a novel notion placing aberrant SUMO-1 conjugation as the main culprit in reperfusion damage, whereas SUMO-2/3 principally serves as a compensatory mechanism during ischaemia to prevent damage. Nevertheless, it also highlights important gaps in the current scientific evidence regarding the role of SUMO, underscoring the need for further investigation.
Gissoni et al. (Fri,) studied this question.