Final Activity Report Summary - KRANG (Kainate receptors and neuronal growth)
Cerebral ischaemia (stroke) is an extreme form of metabolic stress resulting from oxygen and glucose deprivation that most commonly occurs when the blood supply to a part of the brain is suddenly interrupted by occlusion of a vessel. Stroke is the third leading cause of death after coronary heart disease and cancer in the industrialised part of the world, and is also the single most common cause of severe disability.
It is well established that brain ischaemia can cause neuronal death via different signalling cascades. The relative importance and interrelationships between these pathways; however, remain poorly understood. Excitatory ionotropic glutamate receptors (GluRs) have been long time considered as potential targets for antiischaemic drugs. GluRs are integral membrane proteins that mediate the majority of excitatory neurotransmission in the brain. In particular, the kainate type of GluR appears to provide a tractable target for therapeutic intervention. In this project we undertook a study to investigate the role of kainate receptors and the posttranslational modification in ischaemia using both in vivo and in vitro model systems.
We have shown that SUMOylation can regulate kainate receptor (KAR) function. Here we investigated changes in protein SUMOylation and levels of KAR and AMPA receptor subunits and demonstrate that posttranslational modification by SUMO and down-regulation of AMPARs and KARs may play important roles in the pathophysiological response to ischemia.
It is well established that brain ischaemia can cause neuronal death via different signalling cascades. The relative importance and interrelationships between these pathways; however, remain poorly understood. Excitatory ionotropic glutamate receptors (GluRs) have been long time considered as potential targets for antiischaemic drugs. GluRs are integral membrane proteins that mediate the majority of excitatory neurotransmission in the brain. In particular, the kainate type of GluR appears to provide a tractable target for therapeutic intervention. In this project we undertook a study to investigate the role of kainate receptors and the posttranslational modification in ischaemia using both in vivo and in vitro model systems.
We have shown that SUMOylation can regulate kainate receptor (KAR) function. Here we investigated changes in protein SUMOylation and levels of KAR and AMPA receptor subunits and demonstrate that posttranslational modification by SUMO and down-regulation of AMPARs and KARs may play important roles in the pathophysiological response to ischemia.